Abstract
Fluperlapine has been reported to possess anti-schizophrenic and antidepressant properties, with low incidence of extrapyramidal side-effects. In order to get more information about the interactions of fluperlapine with rat brain dopaminergic systems, its binding to striatal D2 receptors, measured ex vivo, and its effects on DA metabolism in different brain areas were investigated. Clozapine and haloperidol served as reference compounds in these investigations. It was found that all three agents blocked D2 receptors and increased DA metabolism. Clozapine and fluperlapine differed from haloperidol in that their potency was much lower. Although occupation of striatal D2 receptors by the two dibenzo-epines developed rapidly, the duration was considerably shorter than that of haloperidol. There was no indication that the two dibenzo-epines had a stronger or longer-lasting effect on limbic or cortical DA metabolism compared to that on the striatum. Both drugs caused a weak increase in striatal DA, whereas haloperidol decreased it. It was concluded that the low incidence of extrapyramidal side-effects of fluperlapine, and also of clozapine, is probably due to their weak and relatively brief action on brain DA systems and not due to a selective action on A10 neurotransmission. The anticholinergic properties of the dibenzo-epines might even further reduce the consequences of their already weak effects on DA systems.
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References
Anden NE (1972) Dopamine turnover in the corpus straitum and the limbic system after treatment with neuroleptic and antiacetylcholine drugs. J Pharm Pharmac 24:905–906
Anden NE, Stock G (1973) Effect of clozapine on the turnover of dopamine in the corpus striatum and in the limbic system. J Pharm Pharmac 25:346–348
Bartholini G (1976) Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system. J Pharm Pharmacol 28:429–433
Bartholini G, Haefely W, Jalfre M, Keller HH, Pletscher A (1972) Effects of clozapine on cerebral catecholaminergic neurone systems. Br J Pharmacol 46:736–740
Bartholini G, Stadler H, Gadea Ciria M, Lloyd KG (1976) The use of the push-pull cannula to estimate the dynamics of acetylcholine and catecholamines within various brain areas. Neuropharmacology 15:515–519
Burki HR (1978) Correlation between 3H-haloperidol binding in the striatum and brain amine metabolism in the rat after treatment with neuroleptics. Life Sci 23:437–442
Burki HR (1979) Biochemical methods for predicting the occurrence of tardive dyskinesia. Commun Psychopharmacol 3:7–15
Burki HR, Ruch W, Asper H, Baggiolini M, Stille G (1974) Effect of single and repeated administration of clozapine on the metabolism of dopamine and noradrenaline in the brain of the rat. Eur J Pharmacol 27:180–190
Burki HR, Asper H, Ruch W, Zuger PE (1978) Bromocriptine, dihydroergotoxine, d-LSD, CF 25–397 and 29–712: effects on the metabolism of the biogenic amines in the brain of the rat. Psychopharmacology 57:227–237
Burki HR, Alder J, Asper H (1980) Binding of thioridazine and clozapine to 3H-haloperidol and 3H-clozapine receptors in the striatum and limbic system of the rat. In: Usdin E, Eckert H, Forrest IS (eds) Phenothiazines and structurally related drugs: basic and clinical studies. Elsevier North Holland, Inc., New York
Burt DR, Creese I, Snyder SH (1976) Properties of 3H-haloperidol and 3H-dopamine binding associated with dopamine receptors in calf brain membranes. Mol Pharmacol 12:800–812
Corrodi H, Hanson LCF (1966) Central effects of an inhibitor of tyrosine hydroxylation. Psychopharmacologia 10:116–125
Eichenberger E (1984) Pharmacology of fluperlapine compared with clozapine. Arzneim Forsch 34:110–113
Fischer-Cornelssen KA (1984) Fluperlapine in 104 schizophrenic patients. Open multicenter trial. Arzneim Forsch 34:125–130
Gianutsos G, Moore KE (1977) Possible significance of clozapine-induced increase in brain dopamine. Res Commun Chem Pathol Pharmacol 17:29–39
Hyttel J (1976) Effects of a single administration of clozapine on mouse brain catecholamines. Acta Pharmacol Toxicol 38:358–365
Iversen LL (1975) Dopamine receptors in the brain. Science 188:1084–1089
Koenig JFR, Klippel RA (1963) The rat brain. Robert E. Krieger Publishing Co., Inc., Huntington, New York
Laverty R, Taylor KM (1968) The fluorometric assay of catecholamines and related compounds: improvements and extensions of the hydroxyindole technique. Anal Biochem 22:269–279
Lehmann J, Langer SZ (1982) Muscarinic receptors on dopamine terminals in the cat caudate nucleus: neuromodulation of [3H]dopamine release in vitro by endogenous acetylcholine. Brain Res 248:61–69
Leysen JE, Gommeren W, Laduron PM (1978) Spiperone: a ligand of choice for neuroleptic receptors. Biochem Pharmacol 27:307–316
Ljungberg T, Ungerstedt U (1979) Evidence that the different properties of haloperidol and clozapine are not explained by differenced in anticholinergic potency. Psychopharmacology 60:303–307
Miller RJ, Hiley CR (1974) Antimuscarinic properties of neuroleptics and drug-induced parkinsonism. Nature 248:596–597
Miller RJ, Hiley CR (1976) Anti-dopaminergic and anti-muscarinic effects of dibenzodiazepines. Naunyn-Schmiedeberg's Arch Pharmacol 292:189–193
Nyback H, Borzecki Z, Sedvall G (1968) Accumulation and disappearance of catecholamines formed from tyrosine-14C in mouse brain; effect of some psychotropic drugs. Eur J Pharmacol 4:395–403
Sayers AC, Burki HR, Ruch W, Asper H (1976) Anticholinergic properties of antipsychotic drugs and their relation to extrapyramidal side-effects. Psychopharmacology 51:15–22
Sedvall G, Nyback H (1972) Effect of clozapine and some other antipsychotic agents on synthesis and turnover of dopamine formed from 14C-tyrosine in mouse brain. Joint E.B.BS-J.C.F.P.B. Workshop Meeting, Jerusalem
Seeman P, Ulpian C (1983) Neuroleptics have identical potencies in human brain limbic and putamen regions. Eur J Pharmacol 94:145–148
Snyder SH, Greenberg D, Yamamura HI (1974) Antischizophrenic drugs and brain cholinergic receptors. Arch Gen Psychiatry 31:58–61
Starke K, Spath L, Lang JD, Adelung C (1983) Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus. Naunyn-Schmiedeberg's Arch Pharmacol 323:298–306
Stawarz RJ, Hill H, Robinson SE, Setler P, Dingell JV, Sulser F (1975) On the significance of the increase in homovanillic acid (HVA) caused by antipsychotic drugs in corpus striatum and limbic forebrain. Psychopharmacoligia 43:125–130
Waldmeier PC, Maitre L (1976) On the relevance of preferential increases of mesolimbic versus striatal dopamine turnover for the prediction of antipsychotic activity of psychotropic drugs. J Neurochem 27:589–597
Westerink BHC (1977) Regional dopamine metabolism in the rat brain. Doctoral Thesis, University of Groningen
Westerink BHC, Korf J (1975) Influence of drugs on striatal and limbic homovanillic acid concentration in the rat brain. Eur J Pharmacol 33:31–40
Wilk S, Watson E, Stanley ME (1975) Differential sensitivity of two dopaminergic structures in rat brain to haloperidol and to clozapine. J Pharmacol Exp Ther 195:265–270
Woggon B, Heinrich K, Kufferle B, Muller-Oerlinghausen B, Poldinger W, Ruther E, Schied HW (1984) Results of a multicenter AMDP study with fluperlapine in schizophrenic patients. Arzneim Forsch 34:122–124
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Burki, H.R. Effects of fluperlapine on dopaminergic systems in rat brain. Psychopharmacology 89, 77–84 (1986). https://doi.org/10.1007/BF00175194
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DOI: https://doi.org/10.1007/BF00175194