Chemistry of Gerontopsychopharmacologic Agents

  • H. Hauth
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 55 / 2)

Abstract

The remarkable progress of medical science in this century has increased average human life expectancy, so that the shift in the age distribution of the population at large has been toward the older end of the spectrum. For this reason medical therapy has become more and more important in the last 20 years. Some reviews concerning pharmacologic and clinical aspects of this field have been published (Sathananthan and Gershon, 1975; Wieck and Blaha, 1976; Hauth and Richardson, 1977; Cole and Branconnier, 1978; Ban, 1978), but up to now no review of the chemical aspects of gerontopsychopharmacologic agents has appeared. The purpose of this chapter, therefore, is to provide the chemical background. As numerous compounds have been claimed to be gerontopsychiatric agents, it is inevitable that only those for which relevant clinical or pharmacologic investigations have been published could be taken into account. Patents have thus rarely been considered, whereas the results of metabolic studies have been included. It is not the purpose of this article to judge pharmacologic and clinical data; the references given are only intended to facilitate an approach to the literature for those with more specifically pharmacologic and clinical interests.

Keywords

Cerebral Blood Flow Ergot Alkaloid Vinca Alkaloid Senile Dementia Isoquinoline Alkaloid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Arcamone, F., Glässer, A.G., Grafnetterova, J., Minghetti, A., Nicolella, V.: Studies on the metabolism of ergoline derivatives. Metabolism of nicergoline in man and animals. Biochem. Pharmarcol. 21, 2205–2213 (1972)Google Scholar
  2. Arcari, G., Bernardi, L., Bosisio, G., Coda, S., Fregnan, G.B., Glässer, A.H.: 10-Methoxyer-goline derivatives as α-adrenergic blocking agents. Experientia 28, 819–820 (1972)PubMedCrossRefGoogle Scholar
  3. Ariens, E.J., Waelen, M.J.G.A., Sonneville, P.F., Simonis, A.M.: The pharmacology of catecholamines and their derivatives. Part I: Relationship between structure and activity as far as the vascular system is concerned. Arzneim. Forsch. 13, 541–546 (1963)Google Scholar
  4. Aurousseau, M.: Pharmacologie comparée des alcaloides indoliques et de leurs dérivés agissant sur la circulation cérébrale et le métabolisme du tissu nerveux. Chim. Ther. 6, 221–234 (1971)Google Scholar
  5. Aurousseau, M., Albert, O., Huet, Y.: First pharmacological data on an indolic compound active on cerebral blood flow: the (±)-epi-21 desethyl eburnamonine. In: Symposium on pharmacology of vinca alkaloids. 2nd Congress of the Hungarian Pharmacological Society. Knoll, J., Fekete, Gy. (eds.), vol. 5, pp. 5–8. Budapest: Akadémiai kiadó 1976aGoogle Scholar
  6. Aurousseau, M., Linée, Ph., Albert, O., Lacroix, P.: Comparative pharmacology of vincamine and two optical antipodes with indolic structure: d- and 1-eburnamonine. In: Symposium on pharmacology of vinca alkaloids. 2nd Congress of the Hungarian Pharmacological Society. Knoll, J., Fekete, Gy. (eds.), vol. 5, pp. 13–16. Budapest: Akadémiai kiadó 1976 bGoogle Scholar
  7. Ban, T.A.: Vasodilators, stimulants and anabolic agents in the treatment of geropsychiatric patients. In: Psychopharmacology — a generation of progress. Lipton, M.A., DiMascio, A., Killam, K.F. (eds.), pp. 1525–1533. New York: Raven Press 1978Google Scholar
  8. Bartoli, G., Frandoli, G., Spreaflco, P.L.: Langzeitbehandlung mit Xanthinolnicotinat (Complamin regard) bei geriatrischen Patienten mit zerebraler Insuffizienz. Therapiewoche 27, 575–585 (1977)Google Scholar
  9. Belpaire, F.M., Bogaert, M.G.: Phospodiesterase inhibition and vascular activity of papaverine metabolites. Arch. Int. Pharmacodyn. Ther. 203, 388–390 (1973)PubMedGoogle Scholar
  10. Bergener, M., Freistein, H.: Die Anwendung der Wittenborn-Psychiatric-Rating Scales in der Gerontopsychiatrie. Arzneim. Forsch. 22, 2058–2063 (1972)Google Scholar
  11. Bernardi, L.: Von den Mutterkorn-Alkaloiden zum Nicergolin. Arzneim.-Forsch. 29 (II), 1204–1206 (1979)Google Scholar
  12. Bernardi, L., Bosisio, G., Elli, C., Patelli, B., Temperilli, A., Arcari, G., Glaesser, H.A.: Ergoline derivatives. Note XIII: α-Adrenergic blocking drugs. Farmaco (Ed. Sci.) 30, 789–801 (1975)Google Scholar
  13. Bernardi, L., Bosisio, G., Croci, M., Elli, C., Temperilli, A., Arcari, G., Falconi, G., Glaesser, A.: Ergoline derivatives with oral, prolonged, α-adrenolytic activity. Farmaco (Ed. Sci.) 33, 118–125(1977)Google Scholar
  14. Bernini, F.P., Muras, I., Maglione, F., Smaltino, F.: L’Azione delia nicergolina sull’ insufficenza del circolo cerebrale da arteriosclerosi. Vallutazione clinica e angioseriografica. Farmaco (Ed. Pr.) 32, 32–46 (1977)Google Scholar
  15. Bessin, P., Gillardin, J.-M., Thuiller, J.: Pharmacologie générale du Fénoxédil (ANP 3548). Nouveau vasodilateur cérébral. Eur. J. Med. Chem. 10, 291–296 (1975)Google Scholar
  16. Bestian, W.: Verfahren zur Herstellung eines Salzes von Theophyllinbasen. Ger. Auslegeschrift 1′02750 (1961)Google Scholar
  17. Bijlsma, U.G., Funcke, A.B.H., Tersteege, H.M., Rekker, R.F., Ernsting, M.J.E., Nauta, W.Th.: The pharmacology of cyclospasmol. Arch. Int. Pharmacodyn. Ther. 105, 145–174 (1956)PubMedGoogle Scholar
  18. Biró, K. Kárpáti, E.: Protective effect of synthetic vinca alkaloids on ischemic anoxia of the brain. In: Symposium on pharmacology of vinca alkaloids. 2nd congress of the Hungarian Pharmacological Society. Knoll, J., Fekete, Gy. (eds.), Vol. 5, pp. 51–54. Budapest: Akadémiai Kiadó 1976Google Scholar
  19. Bölsing, E., Klatte, F., Rosentreter, U., Winterfeldt, E.: Stereoselektive Totalsynthese von Eburnamonin, Eburnamin und Eburnamenin. Chem. Ber. 112, 1902–1912 (1979)CrossRefGoogle Scholar
  20. Boissier, J.R., Ratouis, R., Dumont, C.: Synthesis and pharmacological study of new piperazine derivatives. I. Benzylpiperazines. J. Med. Chem. 6, 541–544 (1963)CrossRefGoogle Scholar
  21. Bombardelli, E., Bonati, A., Danieli, B., Gabetta, A., Martinelli, E.M., Mustich, G.: Decarbomethoxy apocuanzine, a new indole alkaloid from Voacanga chalotiana. Experientia 30, 979–980 (1974)CrossRefGoogle Scholar
  22. Bouvier, J.B., Passeron, O., Chupin, M.P.: Psychometric study of praxilene. J. Int. Med. Res. 2, 59–65 (1974)Google Scholar
  23. Brock, N., Kühas, E., Lorenz, D.: Untersuchungen über Spasmolytica. I. Zur Pharmakologie der Mandelsäureester. Arzneim. Forsch. 2, 165–168 (1952)Google Scholar
  24. Brunei, M.A., Boucherie, A., Badinand, A.: Amides et esters dérivés du naphtalène. Chim Thér. 2, 246–249 (1967)Google Scholar
  25. Bruneton, J. Bouquet, A. Cavé, A.: Alcaloides des écorces de racines de Crioceras dipladeniiflorus. Phytochem. 12, 1475–1480 (1973)CrossRefGoogle Scholar
  26. Bruneton, J., Kan-Fen, Ch., Cavé, A.: La criocerine: Nouvel alcaloide isolé des tiges de Crioceras dipladenitflorus. Phytochem. 14, 569–571 (1975)CrossRefGoogle Scholar
  27. Bürki, H.R., Asper, H., Ruch, W., Züger, P.E.: Bromocryptine, dihydroergotoxine, methyser-gide, d-LSD, CF 25–397, and 29–712: Effects on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacology 57, 227–273 (1978)PubMedCrossRefGoogle Scholar
  28. Buu-Hoi, N.P., Lambelin, G., Roba, J., Jacques, G., Gillet, C.: Amino-alcools et leur préparation. Belg. Patent 755′688 (1971)Google Scholar
  29. Buzas, A., Pierre, R.: Nouveaux dérivés amides de la pipéronyl-pipérazine pharmaceutiquement actifs. French Patent M 7’524 (1970)Google Scholar
  30. Caron-Sigaut, C., Le Men-Olivier, L., Hugel, G., Lévy, J., Le Men, J.: Dérives 14-hydroxyles de la vincadifformine et de la vincamine. Tetrahedron 35, 957–960 (1979)CrossRefGoogle Scholar
  31. Carron, C., Jullien, A., Bucher, B.: Synthesis and pharmacological properties of a series of 2-piperidino alkanol derivatives. Arzneim. Forsch. 21, 1992–1998 (1971)Google Scholar
  32. Cignarella, G., Testa, E.: 2,6-Dialkylpiperazines. V. Synthesis of 2,6-Alkyl-piperazine derivatives structurally related to cinnarizine. J. Med. Chem. 11, 612–615 (1968)PubMedCrossRefGoogle Scholar
  33. Cignarella, G., Pirisoni, G., Lorgia, M., Dorigotti, L.: 2,6-Dialkylpiperazines. VIII. N1-Aryl-alkyl-N4-(2′-pyridyl)-2,6-dimethylpiperazines as adrenolytic and vasodilator agents. Farmaco (Ed. Sci.) 32, 296–302 (1977)Google Scholar
  34. Claassen, V.: Stereospecific divergence in the actions on adrenergic α- and ß-receptors. Bio- chem. Pharmacol. 8, 116 (1961)Google Scholar
  35. Closse, A., Hauser, D.: Evidence for an endogenous dihydroergotamine-like factor in calf and rat brain. Brain Res. 147, 401–404 (1978)PubMedCrossRefGoogle Scholar
  36. Cole, J.O., Branconnier, R.: The therapeutic efficacy of psychopharmacological agents in senile organic brain syndrome. In: Senile dementia — a biomedical approach. Nandy, K. (ed.), pp. 271–286. Amsterdam, New York: Elsevier/North-Holland Biomedical Press 1978Google Scholar
  37. Consolo, S., Fanelli, R., Garattini, S., Ghezzi, D., Jori, A., Ladinsky, H., Marc, V., Samanin, R.: Dopaminergic-cholinergic interaction in the striatum: studies with piribedil. Adv. Neurol. 9, 257–272 (1975)PubMedGoogle Scholar
  38. Cooper, A.J., Magnus, R.V.: A placebo-controlled study of pyritinol (“Encephabol”) in dementia. Pharmatherapeutica 2, 317–322 (1980)PubMedGoogle Scholar
  39. Cornu, F.: Zur Kreislaufphysiologie und Biochemie zerebraler Abbauprozesse und der Verhaltensbeeinflussung von Kranken durch Pharmakotherapie. Wien. Klin. Wochenschr. 81, 426–431 (1969)PubMedGoogle Scholar
  40. Costall, B., Naylor, R.J.: Neuropharmacological studies on the site and mode of action of ET 495. Adv. Neurol. 3, 281–293 (1973)Google Scholar
  41. Costall, B., Naylor, R.J.: Dopamine agonist and antagonist activities of piribedil (ET 495) and its metabolites. Naunyn Schmiedebergs Arch. Pharmacol. 285, 71–81 (1974)Google Scholar
  42. De Feo, G., Giannangeli, M., Piccinelli, D., Sale, P.: Separazione e studio farmacologico dei due enantiomeri del proxazolo. Farmaco (Ed. Sci.) 26, 370–376 (1971)Google Scholar
  43. Depoortere, H., Rousseau, A., Jalfre, M.: Action éveillante de la vincamine chez le rat. Rev. Electroencephalogr. Neurophysiol. Clin. 7, 153–157 (1977)PubMedCrossRefGoogle Scholar
  44. Devic, M.: Un médicament psychotonique, anxiolytique et activateur du métabolisme cérébral en neurologie. J. Méd. Lyon 54, 517–519 (1973)Google Scholar
  45. Dormard, Y., Levron, J.C., Benakis, A.: Pharmacokinetic study of maleate acid of 2-(N,N-di-methylaminoethanol-14C1)-cyclohexylpropionate (cyprodenate) and of N,N-Dimethyl-aminoethanol-14C1 in animals. I. Localisation, distribution, and elimination of 14C-cypro-denate and 14C-dimethylaminoethanol in animals. Arzneim. Forsch. 25, 194–201 (1975 a)Google Scholar
  46. Dormard, Y., Levron, J.C., Le Fur, J.M.: Pharmakokinetic study of maleate acid of 2-(N,N-dimethylaminoethanol-14C1)-cyclohexylpropionate (cyprodenate) and of N,N-dimethyl-aminoethanol-14C1 in animals. II. Study and identification of the metabolites of 14C-cypro-denate and 14C-dimethylaminoethanol in animals. Arzneim. Forsch. 25, 201–207 (1975 b)Google Scholar
  47. Dormard, Y., Levron, J.C., Le Fur, J.M., Adnot, P.: Etude de la distribution, de l’élimination et de la biotransformation du Fénoxédil-14C chez le rat et le porc. Eur. J. Med. Chem. 10, 302–308 (1975 c)Google Scholar
  48. Dyke, S.F.: The Isoquinoline Alkaloids. In: Rodd’s chemistry of carbon compounds IV. Coffey, S. (ed.), Part H, pp. 1–258. Amsterdam, Oxford, New York: Elsevier 1978Google Scholar
  49. Eckert, H., Kiechel, J.R., Rosenthaler, J., Schmidt, R., Schreier, E.: Biopharmaceutical aspects. Analytical methods, pharmakokinetics, metabolism and bioavailability. In: Ergot alkaloids and related compounds. Berde, B., Schild, H.O. (eds.), Handbook of Experimental Pharmacology, Vol. 49, pp. 719–803. Berlin, Heidelberg, New York: Springer 1978Google Scholar
  50. Eidebenz, E. v. Schuh, H.G.: Verfahren zur Herstellung von l-Hexyl-3,7-dimethylxanthin. Ger. Patent 860′217 (1952)Google Scholar
  51. Esanu, A.: Salts of pyridoxine monoesters. US Patent 3′717′636 (1973)Google Scholar
  52. Esposito, G., De Gregorio, M.: Proxazole in cerebrovascular insufficiency. Arzneim. Forsch. 24, 1692–1696 (1974)Google Scholar
  53. Fanchamps, A.: Controlled studies with dihydroergotoxine in senile cerebral insufficiency. In: Geriatric Psychopharmacology, Developments in Neurology. Nandy, K. (ed.), Vol. 3, 195–212, New York: Elsevier North Holland, 1979Google Scholar
  54. Fehr, T., Hauth, H.: A bromo ergot alkaloid. Br. Patent 1′451′904 (1973)Google Scholar
  55. Ferris, S.H., Sathananthan, G., Gershon, S., Clark, C.: Senile dementia treatment with deanol. J. Am. Geriatr. Soc. 25, 241–244 (1977)PubMedGoogle Scholar
  56. Flückiger, E., del Pozo, E.: Influence on the endocrine system. In: Ergot alkaloids and related compounds. Berde, B., Schild, H.O. (eds.), Handbook of Experimental pharmacology Vol. 49, pp. 615–690. Berlin, Heidelberg, New York: Springer 1978Google Scholar
  57. Fontaine, L., Grand, M., Szarvasi, E.: Premiéres comparaisons, in vitro et in vivo, des activités antispasmodiques dans une série de dialcoylaminoesters et étheroxydes. C.R. Hebd. Séances Acad. Sci., Série D 262, 719–721 (1965)Google Scholar
  58. Fontaine, L., Grand, M., Charbert, J., Szarvasi, E., Bayssat, M.: Pharmacologie générale d’une substance nouvelle vasodilatatrice le naftidrofuryl. Chim. Ther. 3, 463–469 (1968)Google Scholar
  59. Fontaine, L., Belleville, M., Lechevin, J.C., Silie, M., Delahaye, J., Boucherai, M.: Etude du métabolisme du naftidrofuryl chez l’animal et chez l’homme. Chim. Ther. 4, 44–49 (1969)Google Scholar
  60. Funcke, A.B.H., Ernsting, M.J.E., Rekker, R.F., Nauta, W.Th.: Untersuchungen über Spasmolytika. I. Mandelsäureester. Arzneim. Forsch. 3, 503–506 (1953)Google Scholar
  61. Garetz, F.K., Baron, J.J., Barron, P.B., Bjork, A.E.: Efficacy of nylidrin hydrochloride in the treatment of cognitive impairement in the elderly. J. Am. Geriat. Soc. 27, 235–236 (1979)PubMedGoogle Scholar
  62. Gerin, J.: Double-blind trial of naftidrofuryl in the treatment of cerebral arteriosclerosis. Br. J. Clin. Pract. 28, 177–178 (1974)PubMedGoogle Scholar
  63. Gesztes, L., Clauder, O.: Vinca minor L. Alkaloidjairól II. A vinkamin újabb lebontási termé-kei. Acta Pharm. Hung. 38, 71–77 (1969)Google Scholar
  64. Giurgea, C.: Piracetam: Nootropic pharmacology of neurointegrative activity. Curr. Dev. Psy-chopharmacol. 3, 221–273 (1976)Google Scholar
  65. Giurgea, C., Salama, M.: Nootropic drugs. Prog. Neuropsychopharmacol. 1, 235–247 (1977)CrossRefGoogle Scholar
  66. Gobert, J.G.: Genèse d’un médicament: Le piracetam. Metabolisation et recherche biochimique. J. Pharm. Belg. 27, 281–304 (1972)Google Scholar
  67. Goi, A., Bruzzese, T., Ghielmetti, G., Riva, M.: Synthesis and pharmacological properties of pyridinecarbonyl derivatives of 7-substituted theophyllines. Chim. Ther. 8, 634–637 (1973)Google Scholar
  68. Guyer, B.M.: Cerebravscular disease in the elderly: Response to Isoxsuprine resinate (Defencin CP) therapy. Clin. Trial J. 15, 49–53 (1978)Google Scholar
  69. Hanna, P.E., O’Dea, R.F., Goldberg, N.D.: Phosphodiesterase inhibition by papaverine and structurally related compounds. Biochem. Pharmacol. 21, 2266–2268 (1972)PubMedCrossRefGoogle Scholar
  70. Hapke, H.-J.: Tierexperimentelle Untersuchungen zur Charakterisierung zentralnervöser Wirkungen von Bencyclan. Arch. Int. Pharmacodyn. Ther. 202, 231–243 (1973)PubMedGoogle Scholar
  71. Hartmann, V., Rödiger, M., Ableidinger, W., Bethke, H.: Dihydroergotoxine: Separation and determination of four components by high performance liquid chromatography. J. Pharm. Sci. 67, 98–103 (1978)PubMedCrossRefGoogle Scholar
  72. Harwart, D.: The treatment of chronic cerebrovascular insufficiency. A double-behind study with pentoxifylline (“Trental” 400″). Curr. Med. Res. Op. 6, 73–84 (1979)CrossRefGoogle Scholar
  73. Hauth, H.: Chemical aspects of ergot derivatives with central dopaminergic activity. In: Dopaminergic ergot derivatives and motor functions. Wenner-Gren Center International Symposium Series. Fuxe, K., Calne, D.B. (eds.), Vol. 31, pp. 23–32. Oxford: Pergamon Press 1979Google Scholar
  74. Hauth, H., Richardson, B.P.: Cerebral vasodilators. Annu. Rep. Med. Chem. 12, 49–59 (1977)CrossRefGoogle Scholar
  75. Hillbom, M.E., Linkola, J., Nikander, P., Wallgren, H.: Effects of pyrithioxine, EMD 17246 and diethanolamine-rutin on acute alcoholic intoxication in rats. Acta Pharmacol. Toxicol. (Kbh) 33, 65–73 (1973)Google Scholar
  76. Hofmann, A., Troxler, F.: 1-Methyl ergotamines and ergocornines. U.S. Patent 3′218′324 (1965)Google Scholar
  77. Hofmann, A., Frey, A., Ott, H.: Verfahren zur Herstellung von Lysergsäurederivaten. Ger. Patent 1′231′708 (1967)Google Scholar
  78. Holtz, P., Langeneckert, W., Palm, D.: Sympathikomimetische Wirkungen von Papaverinderi-vaten. Naunyn Schmiedebergs Arch. Pharmakol. exp. Pathol. 259, 290–306 (1968)Google Scholar
  79. Hotovy, R., Enenkel, HJ., Gillissen, J., Jahn, M., Kraft, H.-G., Müller-Calgan, H., Mürmann, P., Sommer, S., Struller, R.: Zur Pharmakologie des Vitamins B6 und seiner Derivate. 2. Mitteilung: Pyrithioxin. Arzneim. Forsch. 14, 26–29 (1964)Google Scholar
  80. Hoyer, S.: Effects of centrophenoxine on cerebral circulation in geriatric patients. In: Geriatric Psychopharmacology, Developments in Neurology. Nandy, K. (ed.), Vol. 3, 261–274. New York: Elsevier North Holland, 1979Google Scholar
  81. Hüller, H., Amon, I., Peters, R., Schmidt, D.: Zur Pharmakologie von l- und DL-Oxyfedrin. Pharmazie 27, 242–245 (1972)PubMedGoogle Scholar
  82. Hugelin, A. Legrain, Y., Willer, J.C., Clostre, F.: Action exitatrice du pyrisuccidéanol sur la formation réticulaire activatrice. Mécanisme noradrénergique. C.R. Hebd. Séances Acad. Sci. Soc. Biol. 166, 1435–1442 (1972)Google Scholar
  83. Itil, T.M., Soldatos, C., Bozak, M., Ramadanoglu, E., Dayican, G., Morgan, V., Menon, G.N.: CNS effects of ISF-2522, a new nootropic (A phase I safety and CNS efficacy study with quantitative pharmaco-EEG and pharmaco-psychology). Curr. Ther. Res. 26, 525–538 (1979)Google Scholar
  84. Jacquy, J., Noel, G.: Double blind trial with suloctidil, a new vasoactive agent, in elderly patients with psychoorganic brain syndrome. Acta Clin. Belg. 32, 22–26 (1977)PubMedGoogle Scholar
  85. Janssen, P.A.J.: Verfahren zur Herstellung von antihistaminaktiven, in 4-Stellung substituierten 1-Benzhydrylpiperazinen. Ger. Auslegeschrift 1′086′235 (1960)Google Scholar
  86. Jones, R.G., Kornfeld, E.C.: Lithium aluminium hydride reduction of pyridine carboxylic esters: Synthesis of vitamin B6. J. Am. Chem. Soc. 73, 107–109 (1951)CrossRefGoogle Scholar
  87. Kalaus, Gy., Györy, P., Szabó, L., Szántay, Cs.: Synthesis of vinca lakaloids and related compounds. IV. Synthesis of butyl group-containing (±)-vincamine analogue. Acta Chim. Acad. Sci. Hung. 96, 385–391 (1978)Google Scholar
  88. Kan-Fan, Ch., Husson, H.-P., Potier, P.: Plantes malgaches. XVI. La Craspidospermine, nouvel alcaloide de Craspidosperum verticillatum (Apocynacées). Bull. Soc. Chim. Fr. 1976, 1227–1228Google Scholar
  89. Kappert, A.: Untersuchungen über die Wirkung neuer dihydrierter Mutterkornalkaloide bei peripheren Durchblutungsstörungen und Hypertonie. Helv. Med. Acta 16, Suppl. XXII, 5–163 (1949)Google Scholar
  90. Kimura, K., Nagata, A., Miyawaki, H.: The metabolism of bencyclane in rat and man. Xenobiotica 9, 119–127(1979)PubMedCrossRefGoogle Scholar
  91. Kitao, K., Yata, N., Yamazaki, M., Iwane, J., Kamada, A.: Blood concentration and urinary excretion profiles following oral administration of esters of pyrithioxin to dogs. Chem. Pharm. Bull. (Tokyo) 25, 1350–1356 (1977)Google Scholar
  92. Kohlmeyer, K., Blessing, J.: Zur Wirkung von Dihydroergocristin-methansulfonat auf den Hirnkreislauf des Menschen im Akutversuch. Arzneim. Forsch. 28 (II), 1788–1797 (1978)Google Scholar
  93. Komlos, E., Petöcz, L.E.: Pharmakologische Untersuchungen über die Wirkung von N-[3-(2-Benzyl-cycloheptyl-oxy)-propyl]-N,N-dimethylammonium-hydrogenfumarat. Arzneim. Forsch. 20, 1338–1357 (1970)Google Scholar
  94. Koppe, V., Poetsch, E., Schulte, K.: Phényl-4(pyrazolyl-3-akyl)-1-pipérazines substituées. Eur. J. Med. Chem. 10, 154–161 (1975)Google Scholar
  95. Kovách, A.G.B., Sándor, P., Biró, Z. Koltay, E., Mazán, K., Clauder, O.: Chemical structure and pharmacological properties of synthetic vincamine derivatives. Acta Physiol. Acad. Sci. Hung. 36, 307–315 (1969)PubMedGoogle Scholar
  96. Kovalyov, G.V., Nikolov, R., Tyurenkov, I.N., Tsakov, M.: Effect of the analog of cinnarizine AS2 on the cardio-vascular-system. Acta Physiol. Pharmacol. Bulg. 2, 27–31 (1976a); Chem. Abstr. 87, 127′711w (1977)Google Scholar
  97. Kovalyov, G.V., Tyurenkov, I.N., Nikolov, R., Nikolova, M.: Effect of the analog cinnarizine AS2 on peripheral blood circulation. Acta Physiol. Pharmacol. Bulg. 2, 33–39 (1976b); Chem. Abstr. 87, 127′212x (1977)PubMedGoogle Scholar
  98. Kovalyov, G.V., Tyurenkov, J.N., Nikolova, M., Nikolov, R.: Effect of the drug AS2 on the central and peripheral mechanism of vascular tone regulation. Acta Physiol. Pharmacol. Bulg. 2, 42–48 (1976c); Chem. Abstr. 86, 100′959p (1977)PubMedGoogle Scholar
  99. Kraft, H.-G., Fiebig, L., Hotovy, R.: Zur Pharmakologie des Vitamin B6 und seiner Derivate. Arzneim. Forsch. 11, 922–929 (1961)Google Scholar
  100. Kreighbaum, W.E., Kavanaugh, W.F., Comer, W.T., Deitchmann, D.: 3(2H)-Isoquinolones. 1.3-Oxygenated analogs of papaverine as peripheral vasodilators. J. Med. Chem. 15, 1131–1135(1972)PubMedCrossRefGoogle Scholar
  101. Külz, F., Schneider, M.: Über neue gefäßerweiternde Sympathomimetica. Klin. Wochenschr. 28, 535–537 (1950)PubMedCrossRefGoogle Scholar
  102. Kuroda, T.: Synthetic studies of vitamin B6 derivatives. VI. Synthesis of pyridoxine disulfide. Bitamin 30, 431–435 (1964); Chem. Abstr. 62, 10′402c (1965)Google Scholar
  103. Kutney, J.P., Cook, G., Cook, J., Itoh, I., Clardy, J., Fayos, J., Brown, P., Svoboda, G.H.: Studies on vinca alkaloids. The structure of vincarodine. Heterocycles 2, 73–78 (1974)CrossRefGoogle Scholar
  104. Lacroix, P., Quiniou, M.J., Linee, Ph., Le Polies, J.B.: Cerebral metabolic and hemodynamic activities of 1-eburnamonine in the anesthetized dog., Arzneim. Forsch. 29 (II), 1094–1101 (1979)Google Scholar
  105. Lasserre, P., Coppolani, T.: Une étude nationale multiceutique mixte, Trivastal 50 retard. Vie méd. 61, 39–50 (1980)Google Scholar
  106. Lechner, H., Ott, E.: Die Wirkung von Tinofedrin auf Fibrinogen und spontane Thrombozytenaggregation bei Patienten mit zerebraler Insuffizienz. Klin. Wochenschr. 56, 1137–1138 (1978)PubMedCrossRefGoogle Scholar
  107. Lehr, S., Sollberg, G., Schuhmacher, H.: Pharmakogene Erhöhung des Intelligenzniveaus. Überlegungen und eine Doppelblindstudie mit Flurnarizin (Sibelium). Pharmakopsychiatr. Neuropsychopharmakol. 11, 134–146 (1978)Google Scholar
  108. Leuchs, H., Möbis, E.: Verwendung von δ-Chlor-valerolactons zur Darstellung von Säuren und Lactonen. Ber. Dtsch. Chem. Ges. 42, 1228–1238 (1909)CrossRefGoogle Scholar
  109. Levy, J.-C., Apffel, D., Desgroux, L., Pelas, J.: Etudes expérimentales des effets circulatoires et métaboliques cérébraux du Fénoxédil administré par voie digestive. Eur. J. Med. Chem. 10, 297–301 (1975)Google Scholar
  110. Lewis, C., Ballinger, B.R., Presly, A.S.: Trial of levadopa in senile dementia. Br. Med. J. 1978 I, 550Google Scholar
  111. Lindner, E.: Eine Reihe von Verbindungen mit α-sympathikolytischer, peripher gefäßerweiternder und sedierender Wirkung. Arzneim. Forsch. 22, 1445–1448 (1972)Google Scholar
  112. Lloyd-Evans, S., Brocklehurst, J.C., Palmer, M.K.: Piracetam in chronic brain failure. Curr. Med. Res. Op. 6, 351–357 (1979)CrossRefGoogle Scholar
  113. Lörincz, Cs., Szabó, K., Kisfaludy, L.: The synthesis of ethyl apovincaminate. Arzneim. Forsch. 26, 1907 (1976)Google Scholar
  114. Loew, D.M., Van Deussen, E.B., Meier-Ruge, W.: Effects on the central nervous system. In: Ergot alkaloids and related compounds. Berde, B., Schild, H.O. (eds.), Handbook of Experimental Pharmacology, Vol. 49, pp. 421–531. Berlin, Heidelberg, New York: Springer 1978Google Scholar
  115. Loubatiéres, A., Bouyard, P., Klein, M., Alric, R.: Action coronaro-dilatatrice de quelques dérivés de la pipérazine chez le chien anésthésié. C.R. Hebd. Séances Acad. Sci., Soc. Biol. 159, 177–180 (1965)Google Scholar
  116. Makman, M.H., Miskra, R.K., Brown, J.H.: The interactions with dopamine-stimulated adenylate cyclases of caudate nucleus and retina-direct agonist effect of a piribedil metabolite. Adv. Neurol. 9, 213–222 (1975)PubMedGoogle Scholar
  117. Matejcek, M., Knor, K., Piguet, P., Weil, C.: Electroencephalographic and clinical changes as correlated in geriatric patients treated three months with an ergot alkaloid preparation. J. Am. Geriat. Soc. 27, 198–202 (1979)PubMedGoogle Scholar
  118. Meier, C.: Centrophenoxin — ein Geriatrikum mit neurotroper Wirkung. Therapiewoche 23, 3659–3662 (1973)Google Scholar
  119. Mercier, J., Dessaigne, S., Lespagnol, A.: Sur le propriétés coronarodilatrices de dihydroiso-quinoléines possédant un substituant xanthinique. C.R. Hebd. Séances Acad. Sci., Soc. Biol. 167, 90–92 (1973)Google Scholar
  120. Meynaud, A., Grand, M., Belleville, M., Fontaine, L.: Effet du naphtidrofuryl sur le métabolisme énergétique cérébral chez la souris. Thérapie 30, 777–788 (1975)PubMedGoogle Scholar
  121. Miller, R.J., Iversen, L.L.: Stimulation of a dopamine-sensitive adenylate cyclase in homogen-ates of rat striatum by a metabolite of pribedil (ET 495). Naunyn Schmiedebergs Arch. Pharmacol. 282, 213–216 (1974)Google Scholar
  122. Moed, H.D., Van Dijk, J.: Synthesis of β-phenylethylamine derivatives. IV. A new vasodilator. Rec. Trav. Chim. Pays-Bas 75, 1215–1220 (1956)CrossRefGoogle Scholar
  123. Mohler, W., Bletz, I., Reiser, M.: Die Struktur von Ausscheidungsprodukten des 1-Hexyl-3,7-dimethylxanthins. Arch. Pharm. (Weinheim) 299, 448–456 (1966 a)CrossRefGoogle Scholar
  124. Mohler, W., Popendiker, K., Reiser, M.: Resorption, Verteilung, Ausscheidung und Abbau von 1-Hexyl-3,7-dimethylxanthin. Arzneim. Forsch. 16, 1524–1528 (1966b)Google Scholar
  125. Mohler, W., Söder, A.: Zur Chemie und Synthese von 3,7-Dimethyl-l-(5-oxo-hexyl)-xanthin. Arzneim. Forsch. 21, 1159–1160 (1971)Google Scholar
  126. Montaut, J., Martinelle, F., Hazeaux, C.: Action du vadilex injectable dans l’insuffisance circulatoire encéphalique. Ann. Med. Nancy 1974, 1529–1533Google Scholar
  127. Nandy, K.: Experimental studies on centrophenoxine in aging brain. In: Geriatric Psychopharmacology, Developments in Neurology, Nandy, K. (ed.), Vol. 3, pp. 247–260. New York: Elsevier North Holland 1979Google Scholar
  128. Nikolov, R.: Pharmacological studies on derivatives of benzhydrylpiperazine. Farmatsiya (Sofia) 26, 40–45 (1976); Chem. Abstr. 86, 150′351e (1977)Google Scholar
  129. Novák, L., Rohály, J., Szántay, C.: Synthesis of vinca alkaloids and related compounds. VI. Synthesis of eburnamonine and isoeburnamonine. Heterocycles 6, 1149–1156 (1977)CrossRefGoogle Scholar
  130. Novak, H., Schorre, G.: Untersuchungen zum Metabolismus von Pyrithioxin. Arzneim. Forsch. 19, 11–15(1969)Google Scholar
  131. Obermeier, K., Thiemer, K., von Schlichtegroll, A.: Einfluß von Tinofedrin auf den zerebralen Energiestoffwechsel von normotonen, hypotonen und hypoxämischen Ratten nach Carotis-Ver schluß. Arzneim. Forsch. 28 (II), 1354–1360 (1978 a)Google Scholar
  132. Obermeier, K., Niebch, G., Thiemer, K., Vergin, H.: Untersuchungen zu Pharmakokinetik and Metabolismus von Tinofedrin. Arzneim. Forsch. 28 (II), 1360–1367 (1978b)Google Scholar
  133. Ono, K., Katsube, J.: Studies on vasodilators. I. Synthesis and stereochemistry of the metabolites of bencylane. Chem. Pharm. Bull. 27, 1085–1093 (1979)Google Scholar
  134. Oppolzer, W., Hauth, H., Pfaffli, P., Wenger, R.: A new enantioselective total synthesis of natural vincamine via an intramolecular Mannich reaction of a silyl enol ether. Helv. Chim. Acta 60, 1801–1810 (1977)Google Scholar
  135. Palazzo, G., Tavella, M., Strani, G., Silvestrini, B.: 1,2,4-Oxadiazoles, IV. Synthesis and pharmacological properties of a series of substituted aminoalkyl-1,2,4-oxadiazoles. J. Med. Pharm. Chem. 4, 351–367 (1961)Google Scholar
  136. Palios, L.: Ergebnisse der Forschung über Herz- und Kreislaufmittel in den vereinigten Heil-und Nährmittelwerken, Budapest, in der Periode 1965–1968. Wiss. Beitr., Vol. 6, pp. 215–222, Martin-Luther-Univ. Halle-Wittenberg 1969Google Scholar
  137. Pallos, L., Budai, Z. Zólyomi, G.: Basische Aether der 1-substituierten Cycloalkanole. Arzneim. Forsch. 22, 1502–1509 (1972)Google Scholar
  138. Pallos, L., Budai, Z. Zólyomi, G., Komlós, E., Petöcz, L.E.: Basische Aether der 1-substituierten Cycloalkan-1-ole. Therapiewoche 1974, 2825–2826Google Scholar
  139. Paracchini, S., Pesce, E.: Nuovo metodo di sintesi parziale della vincamina e di alcaloidi indolici correlati. Farmaco (Ed. Sci.) 33, 573–582 (1978)Google Scholar
  140. Petrova, L.A., Beltsova, N.N.: Synthesis of sulfar containing pyridoxin derivatives. Zh. Obshch. Khim. 32, 274–277 (1962); Chem. Abstr. 57, 16′543h (1962)Google Scholar
  141. Pfäffli, P., Hauth, H.: Additionsreaktionen an der alicyclischen Doppelbindung von Eburna-menin und Apovincamin. Helv. Chim. Acta 61, 1682–1695 (1978)CrossRefGoogle Scholar
  142. Pfaffli, P., Oppolzer, W., Wenger, R., Hauth, H.: Stereoselektive Synthese von optisch aktivem Vincamin. Helv. Chim. Acta 58, 1131–1145 (1975)PubMedCrossRefGoogle Scholar
  143. Pinza, M., Dorigotti, L., Pifferi, G.: Synthesis, adrenolytic and vasodilator properties of new 2,2,6-trimetylpiperazines. Eur. J. Med. Chem. 11, 395–398 (1976)Google Scholar
  144. Poignant, J.-C., Lejeune, F., Malecot, E., Petitjean, M., Régnier, G., Canevari, R.: Effets comparés du piribédil et de trois de se métabolites sur le systéme extrapyramidal du rat. Expe-rimentia 30, 70–71 (1974)CrossRefGoogle Scholar
  145. Poignant, J.-C., Gressier, H., Petitjean, M., Regnier, G., Canevari, R.: A new central direct dopaminergic stimulant: 1-(Coumaran-5-yl-methyl)-4-(2-thiazolyl)piperazine hydrochloride (S 3608). Experimentia 31, 1204–1205 (1975)CrossRefGoogle Scholar
  146. Popendiker, K., Boksay, J., Bollmann, V.: Zur Pharmakologie des neuen peripheren Gefaßdi-latators 3,7-Dimethyl-l-(5-oxohexyl)-xanthin. Arzneim. Forsch. 21, 1160–1171 (1971)Google Scholar
  147. Porsche, E., Stefanovich, V.: Der Einfluß von Pentifyllin und Theophyllin auf die Reaktionskinetik von Katecholamin-stimulierbarer ATPase aus Rattenhirn. Arzneim. Forsch. 29 (II), 1089–1092 (1979)Google Scholar
  148. Probst, G., Keiser, G.: Klinische Prüfung eines neuen Vasodilatans (Dihydrin) bei zerebralen Durchblutungsstörungen und apoplektischen Insulten. Praxis 58, 1653–1658 (1969)PubMedGoogle Scholar
  149. Prudhommeaux, E., Ernouf, G., Foussard-Blanpin, O., Viel, C.: Nouveaux analogues structuraux de la papavérine: benzyl-3 diméthoxy-6,7 isoquinoléines di- et tétra-hydrogénées. Eur. J. Med. Chem. 10, 19–28 (1975)Google Scholar
  150. Ramos, A.O., Ramos, L., Zanini, A.C., Slemer, O.: On the pharmacology of 1-hexyl-3,7-di-methylxanthine. Arch. Intern. Pharmacodyn. 153, 430–435 (1965)Google Scholar
  151. Rao, D.B., Georgiev, E.L., Paul, P.D., Guzmann, A.B.: Cyclandelate in the treatment of senile mental changes: A double-blind evaluation. J. Am. Ger. Soc. 25, 548–551 (1977)Google Scholar
  152. Ratouis, R., Boissier, J.R., Dumont, C.: Synthesis and pharmacological study of new piperazine derivatives. II. Phenethylpiperazines. J. Med. Chem. 8, 104–107 (1965)PubMedCrossRefGoogle Scholar
  153. Regnier, G.L., Canevari, R.J., Laubie, M.J., De Douarec, J.C.: Synthesis and vasodilator activity of new piperazine derivatives. J. Med. Chem. 11, 1151–1155 (1968)PubMedCrossRefGoogle Scholar
  154. Regnier, G., Canevari, R., Le Douarec, J.-C., Laubie, M.: Dépresseurs du systeme nerveux central. Etude de nouveaux dérivés de la purine. Chim. Thér. 7, 192–205 (1972)Google Scholar
  155. Ritchie, J.M.: Central nervous system stimulants. The xanthines. In: The pharmacological basis of therapeutics. Goodmann, L.S., Gilmann, A. (eds.), pp. 367–378. New York: Macmillan 1975Google Scholar
  156. Roba, J., Roncucci, R., Lambelin, G.: Pharmacological properties of suloctidil. Acta Clin. Belg. 32, 3–7 (1977)Google Scholar
  157. Rutschmann, J., Stadler, P.A.: Chemical background. In: Ergot alkaloids and related compounds. Berde, B., Schild, H.O. (eds.), Handbook of Experimental Pharmacology, Vol. 49, pp. 29–85. Berlin, Heidelberg, New York: Springer 1978Google Scholar
  158. Saiko, O., Klug, R.: Verfahren zur Herstellung eines schwefelhaltigen Pyridinderivates. Ger. Offenlegungsschrift 24′59′334 (1976)Google Scholar
  159. Saletu, B., Grunberger, J., Linzmayer, L.: Bestimmung der enzephalotropen, psychotropen und pharmakodynamischen Eigenschaften von Nicergolin mittels quantitativer Pharmakoelek-troenzephalographie und psychometrischer Analyse. Arzneim. Forsch. 29 (II), 1257–1261 (1979)Google Scholar
  160. Saletu, B., Grunberger, J., Saletu, M., Mader, R., Volavka, J.: Treatment of the alcoholic organic brain syndrome with EMD 21,657. A derivative of a pyritinol metabolite: Double-blind clinical, quantitative EEG and psychometic studies. Int. Pharmacopsychol. 13, 177–192 (1978 a)Google Scholar
  161. Saletu, M., Grunberger, J., Saletu, B., Mader, R.: Accelerated remission of the alcoholic organic brain syndrome with EMD 21,657. Double-blind clinical and psychometic trials. Arzneim. Forsch. 28 (II), 1525–1527 (1978b)Google Scholar
  162. Sathananthan, G.L., Gershon, S.: Cerebral vasodilators — a review. In: Aging. Gershon, S., Raskin, A. (eds.), Vol. 2, pp. 155–168. New York: Ravens Press 1975Google Scholar
  163. Saus, A., Posselt, K.: Synthese von radioaktiv markiertem Tinofedrin. Arzneim. Forsch. 30 (I), 917–918 (1980)Google Scholar
  164. Schöpf, C., Kunz, K.J.: Pharmacologically valuable stereoisomers of certain aminoalcohols and their salts. US Patent 2′661′372 (1953)Google Scholar
  165. Scholing, W.E., Clausen, H.D.: Langzeitbehandlung des neurovaskulären Psychosyndroms mit Trivastal. Med. Klin. 70, 1522–1527 (1975)PubMedGoogle Scholar
  166. Serchi, G.: Ricerche sulle dimetil-xantine. Nota V: Derivati alchilici e cycloalchilici della teofil-lina e della teobromina a cinque e sei atomi di carbonio. Chimica (Milan) 40, 451–459 (1964); Chem. Abstr. 62, 13′145c (1965)Google Scholar
  167. Shamma, M.: The isoquinoline alkaloids. Chemistry and pharmacology. In: Organic chemistry, a series of monographs. Blomquist, A.T., Wassermann, H. (eds.), Vol. 25, 44–152, New York, London: Academic Press 1972Google Scholar
  168. Shaw, T.G., Meyer, J.S.: Double-blind trial of oral papaverine in chronic cerebrovascular ischemia. Angiology 29, 839–851 (1978)PubMedCrossRefGoogle Scholar
  169. Silvestrini, B., Pozzatti, C.: Pharmacological properties of 3-α-phenyl-5-β-diethylaminoethyl-1,2,4-oxazole citrate. Arzneim. Forsch. 13, 798–802 (1963)Google Scholar
  170. Simon, L., Pórszász, J., Gibiszerkatalin, P., Talpas, S.G.: Physikochemische Eigenschaften und Membranwirkung spasmolytisch wirksamer Isochinolin- bzw. 1,2,3,4-Tetrahydroisochino-linderivate. Pharmazie 32, 235–239 (1977)PubMedGoogle Scholar
  171. Solti, F., Iskum, M., Czakó, E.: Effect of ethyl apovincaminate on the cerebral circulation. Studies in patients with obliterative arterial disease. Arzneim. Forsch. 26, 1945–1947 (1976)Google Scholar
  172. Soudijn, W., van Wijngaarden, J.: The metabolism and excretion of cinnarizine by rats. Life Sci. 1968, 231–238Google Scholar
  173. Soulairac, A.: Etude des actions psychiques et psychomotrices du fipexide (Vigilor). Gaz. Méd. France 82, 3547–3550 (1975)Google Scholar
  174. Spehr, W.: Zur Zeitgestalt des Elektroenzephalogramms unter Tinofedrin. Arzneim. Forsch. 28 (II), 1312–1313 (1978)Google Scholar
  175. Stadler, P., Depoortere, H.: Nouveaux amides peptidiques d’acides 6-alkyl-ergoline-8-carboxyliques, leur préparation et leur application comme médicaments. Belg. Patent 833′835 (1976)Google Scholar
  176. Stadler, P., Hauth, H., Wersin, G., Guttmann, S., Hofmann, A., Stütz, P., Wilems, H.: Heterocyclische Verbindungen und Verfahren zu ihrer Herstellung. Ger. Offenlegungsschrift l′795′022 (1971)Google Scholar
  177. Staessen, A.J.: Treatment of circulatory disturbances with flunarizine and cinnarizine. A multicentre, double-blind and placebo-controlled evaluation. VASA 6, 59–71 (1977)PubMedGoogle Scholar
  178. Stanton, H.C., Dungan, K.W., Lish, P.M.: Some pharmacological comparisons of isoxsuprine with two structural analogues. Fed. Proc. 24, 612 (1965)Google Scholar
  179. Stoll, A., Hofmann, A.: Die Dihydroderivate der natürlichen linksdrehenden Mutterkornalkaloide. Helv. Chim. Acta 26, 2070–2081 (1943)CrossRefGoogle Scholar
  180. Stütz, P.L., Stadler, P.A., Vigouret, J.-M., Jaton, A.L.: Ergot alkaloids. New ergolines as selective dopaminergic stimulants. J. Med. Chem. 21, 754–757 (1978)PubMedCrossRefGoogle Scholar
  181. Sweet, R.D., Wasterlain, C.G., McDowell, F.H.: Piribedil, a dopamine agonist, in Parkinson’s disease. Clin. Pharmacol. Ther. 16, 1077–1082 (1974)PubMedGoogle Scholar
  182. Szabó, L., Kalaus, G., Nógradi, K., Szánty, C.: Synthesis of vinca alkaloids and related compounds. IX. Attempted assymetric synthesis of vincamine-5-carboxylic acid isopropylester. Acta Chim. Acad. Sci. Hung. 99, 73–80 (1979)Google Scholar
  183. Szántay, C., Szabó, L., Kalaus, G.: Synthesis of vinca alkaloids and related compounds. II. Stereoselective and enantioselective synthesis of (+)-vincamine. Tetrahedron 33, 1803–1808 (1977)CrossRefGoogle Scholar
  184. Szarvasi, E., Bayssat, M., Fontaine, L., Grand, M.: Quelques nouvelles structures naphtaléni-ques à activité antispasmodique. Bull. Soc. Chim. France 1966, 1838–1846Google Scholar
  185. Szarvasi, E., Bayssat, M., Fontaine, L., Grand, M.: Diamines di-tertiaires naphtaléniques. Chim. Ther. 2, 407–409 (1967)Google Scholar
  186. Szporny, L.: Pharmacologie de la vincamine et de ses dérivés. Actual. Pharmacol. (Paris) 29, 88–117(1977)Google Scholar
  187. Taylor, W.I.: The pentaceras and the eburnamine (hunteria)-vincamine alkaloids. In: The alkaloids. Manske, R.H.F. (ed.), Vol. 8, pp. 249–268. New York, London: Academic Press 1965Google Scholar
  188. Taylor, W.I.: The eburnamine-vincamine alkaloids. In: The alkaloids. Manske, R.H.F. (ed), Vol. 11, pp. 125–143. New York, London: Academic Press 1968Google Scholar
  189. Taylor, W.I., Farnsworth, N.R. (eds.): The vinca alkaloids. New York: Dekker 1973Google Scholar
  190. Teubner, W.: Isoxsuprin (Vasoplex). Literaturübersicht über experimentelle und klinische Ergebnisse. Fortschr. Med. 90, 517–521 (1972)PubMedGoogle Scholar
  191. Theis, H., Lehrach, F., Müller, R.: A 5-year review of clinico-experimental and therapeutic experience with pentoxifylline. Pharmatherapeutica 2, Suppl. 1., 150–160 (1978)Google Scholar
  192. Thiele, K., Schimassek, U., von Schlichtegroll, A.: Neue herzwirksame ß-Aminoketone. Synthese und Betrachtungen über Zusammenhänge zwischen pharmakologischer Wirkung und Konstitution neuer Mannich-Basen I. Arzneim. Forsch. 16, 1064–1067 (1966)Google Scholar
  193. Thiele, K., Koberstein, E., Nonnenmacher, G.: Neue herzwirksame ß-Aminoketone. II. Ein physikalisch-chemischer Beitrag zur Charakterisierung von Oxyfedrin. Arzneim. Forsch. 18, 1255–1263 (1968)Google Scholar
  194. Thiele, K., Posselt, K., Gross, A., Schuler, A.W.: Über neue basische Thienylalkanderivate mit coronargefaßerweiternder Wirkung. Chim. Ther. 4, 228–233 (1969)Google Scholar
  195. Thiele, K., Posselt, K., Offermanns, H.: Zur Synthese der zerebroaktiven Substanz Tinofedrin. Arzneim. Forsch. 28 (II), 2047–2048 (1978)Google Scholar
  196. Thiele, K., Posselt, K., Offermanns, H., Thiemer, K.: Neue zerebral wirksame basische Dithie-nyl-Verbindungen. Arzneim. Forsch. 30 (I), 747–757 (1980a)Google Scholar
  197. Thiele, K., Posselt, K., Heese, J., Engel, J.: Spektroskopische Charakterisierung von Tinofedrin. Arzneim. Forsch. 28 (II), 1057–1059Google Scholar
  198. Thiemer, K., Stroman, F., Szelenyi, I., von Schlichtegroll, A.: Pharmakologische Wirkung von Tinofedrin auf die zerebrale und periphere Hämodynamik des Hundes. Arzneim. Forsch. 28 (II), 1343–1354 (1978)Google Scholar
  199. Thiery, E., Otte, G., Vander Eeken, H.: Comparative study of the clinical effect of vincamine versus papaverine given parenterally in the acute phase of stroke. Arzneim. Forsch. 29 (I), 571–574 (1979)Google Scholar
  200. Thuillier, G.: Dérivés des acides aryloxyacétiques à activité neurotrope. Chim. Ther. 1, 82–86 (1966)Google Scholar
  201. Thuillier, G., Rumpf, P.: Préparation de nouveaux esters et amides basiques des acides qui agissent comme régulateurs de croissance des végétaux. Relations entre la structure et l’activité biologique. Bull. Soc. Chim. Fr. 1960, 1786–1794Google Scholar
  202. Thuillier, G., Marlier, S, Saville, B., Rumpf, P.: Préparation de nouveaux esters et amides basiques des acides qui agissent comme régulateurs de croissance des végétaux. II. Isostères soufrés et azotés. Bull. Soc. Chim. Fr. 1963a, 1084–1086Google Scholar
  203. Thuillier, G., Dumont, J.-M., Vilar, A., Rumpf, P.: Préparation de nouveaux esters et amides basiques des acides qui agissent comme régulateurs de croissance des végétaux. III. Amides. Bull. Soc. Chim. Fr. 1963 b, 1087–1090Google Scholar
  204. Thuillier, G., Geffroy, F., Bessin, P., Thuillier, J.: Synthèse d’aryloxyacétamides tertiaires. Va-sodilateurs cérébraux et périphériques. Eur. J. Med. Chem. 10, 286–290 (1975)Google Scholar
  205. Valette, R.: ß-Cyclohexylpropionsäure-2-dimethylamino-äthylester und seine Salze sowie Verfahren zu deren Herstellung. Ger. Auslegeschrift 1′283′233 (1968)Google Scholar
  206. Van Dijk, J., Moed, H.D.: Synthesis of ß-phenylethylamine derivatives VII. The enantiomers of erythro-l-(4′-hydroxyphenyl)-2-(1″-methyl-2″-phenoxyethylamino)-propanol-l. Rec. Trav. Chim. Pays-Bas 80, 573–587 (1961)CrossRefGoogle Scholar
  207. Van Dijk, J., Keizer, V.G., Moed, H.D.: Synthesis of ß-phenyläthylamine derivatives. VIII. Four diastereomers of l-(4′-hydroxy-phenyl)-2-(1″-methyl-3″-phenylpropylamino)-propanol. Rec. Trav. Chim. Pays Bas 82, 189–201 (1963)CrossRefGoogle Scholar
  208. Van Dijk, J., Keizer, V.G., Peelen, J.F., Moed, H.D.: Synthesis of ß-phenylethylamine derivatives. IX. The enantiomers and diastereomers of N-phenoxyalkyl-ß-(4-hydroxyphenyl) ethylamine derivatives. Rec. Trav. Chim. Pays Bas 84, 521–539 (1965)CrossRefGoogle Scholar
  209. Van Schepdael, J.: Etude clinique de l’action du suloctidil sur la maladie cérébro-vasculaire chronique de la personne agée. Ars Med. 32, 1505–1518 (1977)Google Scholar
  210. Vereczkey, L., Szporny, L.: Metabolism of ethyl apovincaminate in the rat. Arzneim. Forsch. 26, 1933–1938 (1976)Google Scholar
  211. Vereczkey, L., Czira, G., Tamás, J., Szentirmay, Z., Botár, Z., Szporny, L.: Pharmacokinetics of vinpocetine in humans. Arzneim. Forsch. 29 (I), 957–960 (1979)Google Scholar
  212. Vigano, V., Paracchini, S., Piacenza, G., Pesce, E.: Metabolismo della vincamina nel ratto. Farmaco (Ed. Sci.) 33, 583–594 (1978)Google Scholar
  213. Waelen, M.J.G.A., Sonneville, P.F., Ariens, E.J., Simonis, A.M.: The pharmacology of catecholamines and their derivatives. Part. II: An analysis of the actions on blood flow and oxygen exchange in skin and muscle. Arzneim. Forsch. 14, 11–19 (1964)Google Scholar
  214. Walter, L.A., Hunt, W.H., Fosbinder, R.J.: ß-(2- and 4-Pyridylalkyl)-amines. J. Am. Chem. Soc. 63, 2771–2773 (1941)CrossRefGoogle Scholar
  215. Wieck, H.H., Blaha, L.: Therapeutische Möglichkeiten bei zerebrovaskulärer Insuffizienz. Therapiewoche 26, 5282–5290 (1976)Google Scholar
  216. Witzmann, H.K., Blechacz, W.: Zur Stellung von Vincamin in der Therapie zerebrovaskulärer Krankheiten und zerebraler Leistungsminderungen. Arzneim. Forsch. 27 (I), 1238–1247 (1977)Google Scholar
  217. Wright, H.B., Martin, D.L.: Hypocholesteremic agents. IV. Some substituted piperazines. J. Med. Chem. 11, 390–391 (1968)PubMedCrossRefGoogle Scholar
  218. Zikan, V., Semonský, M.: Mutterkornalkaloide XVI. Einige N-(D-6-Methylisoergolenyl-8)-, N-(D-6-Methylergolenyl-8)- und N-(D-6-Methylergolin(I)-yl-8)-N′-substituierte Harnstoffe. Coll. Czech. Chem. Commun. 25, 1922–1928 (1960)Google Scholar
  219. Zikan, V., Semonsky, M.: Mutterkornalkaloide 31. Mitteilung: Ein Beitrag zur Herstellung von N-(D-6-Methyl-8-isoergolenyl)-N′,N′-diäthylharnstoff. Pharmazie 23, 147–148 (1968)Google Scholar
  220. Zikan, V., Semonský, M., Rězábek, K., Auskova, M., Seda, M.: Ergot alkaloids XL. Some N-(D-6-methyl-8-isoergolin-I-yl)- and N-(D-6-methyl-8-isoergolin-n-yl)-N′-substituted ureas. Coll. Czech. Chem. Commun. 37, 2600–2605 (1972)Google Scholar
  221. Zikolova, S., Ninov, K.: Analogs of N1-benzhydryl-N4-cinnamylpiperazine (cinnarizine). I. N4-substituted-N1-cinnamylpiperazines. Tr. Nauchnoizsled. Khim.-Farm. Inst. 8, 49–58 (1972a); Chem. Abstr. 78, 147′914v (1973)Google Scholar
  222. Zikolova, S., Ninov, K.: Analogs of N1-benzhydryl-N4-cinnamylpiperazine (cinnarizine). II. N1-substituted-N4-benzhydryl-piperazines. Tr. Nauchnoizsled. Khim.-Farm. Inst. 8, 59–67 (1972 b); Chem. Abstr. 78, 147′908w (1973)Google Scholar
  223. Zikolova, S., Ninov, K.: Analogs of N1-benzhydryl-N4-cinnamylpiperazine (cinnarizine). III. N-Cinnamoyl- and N[(cinnamoyloxy)alkyl]piperazines. Tr. Nauchnoizsled. Khim.-Farm. Inst. 9, 125–134 (1974); Chem. Abstr. 83, 79′194 m (1975)Google Scholar
  224. Zima, O., Schorre, G.: Derivatives of vitamin B6. U.S. Patent 3′010′966 (1961)Google Scholar
  225. Züger, P.E., Vigouret, J.-M., Loew, D.M.: Inhibition of reserpine-induced PGO waves in the cat by ergot derivatives. Experientia 34, 637–639 (1978)PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1981

Authors and Affiliations

  • H. Hauth

There are no affiliations available

Personalised recommendations