Cannabinoid Geometry and Biological Activity

  • Raphael Mechoulam
  • W. A. Devane
  • R. Glaser


Since the isolation and structure elucidation of delta-9-THC by our group in 1964, numerous investigations have addressed the structure-activity relationships (SAR) in the cannabinoid series. The rules established in the 1970s have mostly withstood the erosion of time. However, the SAR rules as regards stereochemistry were developed much later. It was shown that in THC-type cannabinoids activity resides exclusively in the (−)cannabinoids with the 6aR, 10aR stereochemistry, as found in natural (−) delta-9-THC. This important observation was one of the factors that led to research that culminated in the identification of cannabinoid receptors. X-ray crystallography and detailed NMR investigation have made possible the establishment of the geometry of the active cannabinoids both in the solid-state and in solution. This geometry is presented now in some detail.


Adenylate Cyclase Drug Discrimination Inhibit Adenylate Cyclase Adenylate Cyclase Assay Stereochemical Requirement 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Mechoulam, R. and Edery, H., Structure-activity relationships in the cannabinoid series, in Marijuana.-Chemistry, Pharmacology, Metabolism and Clinical Effects, Mechoulam, R., Ed., Academic Press, New York, 1973.Google Scholar
  2. 2.
    Dewey, W. L., Martin, B. R., and May, E. L., Cannabinoid stereoisomers: pharmacological effects, in Handbook of Stereoisoniers: Drugs in Psychchopharmacology, Smith, D. F., Ed., CRC Press. Boca Raton, FL, 1984, 317.Google Scholar
  3. 3.
    Razdan, R. K., Structure-activity relationships in cannabinoids, Pharmacol. Rev., 38, 75, 1986.PubMedGoogle Scholar
  4. 4.
    Mechoulam, R., Lander, N., Srebnik, M., Breuer, A., Segal, M., Feigenbaum, J. J., Järbe, T. U. C., and Cons-roe, P., Stereochernical requirements for cannabirnimetic activity, in Structure-Activity Relationships of the Cannabinoids, Rapaka, R. S. and Makriyannis, A., Eds., NIDA Research Monograph 79, Rockville, MD, 1987, 15.Google Scholar
  5. 5.
    Martin, B. R., Cellular effects of cannabinoids, Pharmacol. Rev., 38, 45, 1996.Google Scholar
  6. 6.
    Dewey, W. L., Cannabinoid pharmacology, Pharmacol. Rev., 38, 151, 1986.PubMedGoogle Scholar
  7. 7.
    Paton, W. D. M. and Pertwee, R. G., The pharmacology of Cannabis in animals, in Marijuana: Chemistry, Pharmacology, Metabolism and Clinical Effects, Mechoulam, R., Ed., Academic Press, New York, 1973.Google Scholar
  8. 8.
    Grunfeld, Y. and Edery, H., Psychopharmacological activity of the active constituents of hashish and some related cannabinoids, Psycholpharmacologia, 14, 200, 1969.CrossRefGoogle Scholar
  9. 9.
    Walton, R. R, Marijuana, America’s New Drug Problem, J.B. Lippincott, Philadelphia, 1938, 168.Google Scholar
  10. 10.
    Martin, B. R., Balster, R. L., Razdan, R. K., Harris, L. S., and Dewey, W. L., Behavior comparisons of the stereoisomers of tetrahydrocannabinols, Life Sci., 29, 565, 1981.PubMedCrossRefGoogle Scholar
  11. 11.
    Pertwee, R. G., The ring test: a quantitative method for assessing the cataleptic effect of Cannabis in mice, Br. J. Pharmacol., 46, 753, 1972.PubMedCrossRefGoogle Scholar
  12. 12.
    Järbe, T. U. C., Johansson, J. O., and Henriksson, B. G., Characteristics of tetrahydrocannabinol produced discrimination in rats, Psycholpharmacologia, 48, 181, 1976.CrossRefGoogle Scholar
  13. 13.
    Järbe, T. U. C., Swedberg, M. D. B., and Mechoulam, R., A repeated tests procedure to assess onset and duration of the cue properties of (-)-delta-9- THC, (-)-delta-8-THC and (+)-delta-g-THC, Psychopharmacologia, 75, 152, 198 1.Google Scholar
  14. 14.
    Molder, D. J., Nelson, D. B., Harris, L. S., and Rosencrans, J. A., The role of benzodiazepine receptors in the discriminative stimulus properties of delta-9-THC, Life Sci., 38, 1581, 1986.CrossRefGoogle Scholar
  15. 15.
    Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S., and Howlett, A. C., Determination and characterization of a cannabinoid receptor in rat brain, Mol. Pharmacol., 34, 605, 1988.PubMedGoogle Scholar
  16. 16.
    Howlett, A. C., Bidaut-Russell, M., Devane, W. A., Melvin, L. S., Johnson, M. R., and Herkenham, M., The cannabinoid receptor: biochemical, anatomical and behavioral characterization, Trends Neurosci., 13, 420, 1990.PubMedCrossRefGoogle Scholar
  17. 17.
    Johnson, M. R. and Melvin, L. S., The discovery of nonclassical cannabinoid analgetics, in Cannabinoids as Therapeutic Agents, Mechoulam, R., Ed., CRC Press, Boca Raton. FL, 1986.Google Scholar
  18. 18.
    Houry, S., Mechoulam, R., Fowler, P. J., Macko, E., and Loev, B., Benzoxocin and benzoxonin derivatives: novel groups of terpenophenols with CNS activity, J. Med. Chem. 17. 287, 1974.PubMedCrossRefGoogle Scholar
  19. 19.
    Houry, S., Mechoulam, R., and Loev, B., Benzoxocin and benzoxonin derivatives: novel groups of terpenophenols with CNS activity, a correction, J. Med. Chem., 18, 951, 1975.PubMedCrossRefGoogle Scholar
  20. 20.
    Bell, M. R. et al., Antinociceptive (aminoalkyl) indoles, J. Med. Chem., 34, 1099, 1991.PubMedCrossRefGoogle Scholar
  21. 21.
    Haubrich, D. R. et al., Pharmacology of pravadoline: a new analgesic agent, J.Pharmacol. Exp. Ther, 255, 511, 1990.PubMedGoogle Scholar
  22. 22.
    Banerjee, S. R, Mechoulam, R., and Snyder, S. H., Cannabinoids: influence on neurotransmitter uptake in rat brain synaptosomes, J. Pharmacol. Exp. Ther, 194, 74, 1975.PubMedGoogle Scholar
  23. 23.
    Seltzman, H. H., Hsieh, Y-A., Pitt, C. G., and Reggio, R H., Synthesis of rotationally restricted THC ethers, J. Org . Chem., 56, 1549, 1991.CrossRefGoogle Scholar
  24. 24.
    Matsumoto, K., Stark, R, and Meister, R. G., 1-Amino-and 1-mercapto-7,8,9, 10-tetrahydro-6H-dibenzo[b,dlpyrans, J. Med. Chem., 20, 17, 1977.PubMedCrossRefGoogle Scholar
  25. 25.
    Agurell, S., Pharmacokinetics and metabolism of delta-1-THC and other cannabinoidswith emphasis on man, Pharmacol. Rev., 38, 21, 1986.PubMedGoogle Scholar
  26. 26.
    Harvey, D. J. and Paton, W. D. M., Metabolism of the cannabinoids, Rev. Biochem. Toxicol., 6, 221, 1984.Google Scholar
  27. 27.
    Lemberger, L., Crabtree, R. E., and Rowe, H.M., 11-Hydroxy-delta-9-THC: pharmacology, disposition and metdbolism of a major metabolite of marihuana in man, Science, 177, 62, 1972.Google Scholar
  28. 28.
    Mechoulam, R., Ben-Zvi, Z., Agurell, S., Nilsson, 1. M., Nilsson, J. L. G., Edery, H.,and Grunfeld, V., Delta-6-THC-7-oic-acid, an urinary delta-6-THC metabolite: isolation and synthesis, Experientia, 29, 1193, 1973.Google Scholar
  29. 29.
    Burstein, S. H., Hull, K., Hunter, S. A., and Latham, V., Cannabinoids and pain responses: a possible role for prostaglandins, FASEB, 2, 3022, 1988.Google Scholar
  30. 30.
    Hollister, L. E., Structure-activity relationships in man of cannabis constituents, and homologs and metabolites of delta-9-THC, Pharmacol. Rev., 11, 3, 1974.CrossRefGoogle Scholar
  31. 31.
    Mechoulam, R., Feigenbaum, J. J., Lander, N., Segal, M., Jiirbe, T. U. C., Hiltunen, A. J., and Consroe, P., Enantiomeric cannabinoids: stereospecificity of psychotropicactivity, Experientia, 44, 762, 1988.PubMedCrossRefGoogle Scholar
  32. 32.
    Mechoulam, R., Lander, N., Breuer, A., and Zahalka, J., Synthesis of the individual, pharmacologically distinct, enantiomers of a tetrahydrocannabinol derivative, Tetrahedron: Asymmetry, 1, 315, 1990.CrossRefGoogle Scholar
  33. 33.
    Järbe, T. U. C., Hiltunen, A. J., and Mechoulam, R, Stereospecificity of the discriminative stimulus functions of the dimethylheptyl homologs of 11-OH-delta-8tetrahydrocannabinol in rats and pigeons, J. Pharmacol. Exp. Ther., 250, 1000, 1989.PubMedGoogle Scholar
  34. 34.
    Little, P. J., Compton, D. R., Mechoulam, R., and Martin, B., Stereochernical effectsof 11-OH-delta-8-THC-dimethylheptyl in mice and dogs, Pharmacol. Biochem. Behan, 32, 661, 1989.CrossRefGoogle Scholar
  35. 35.
    Thomas, B. F., Compton, D. R., and Martin, B. R., Characterization of the lipophilicity of natural and synthetic analogs of delta-9-THC and its relationship to pharmacological potency, J. Pharmacol. Exp. Ther., 255, 624, 1990.PubMedGoogle Scholar
  36. 36.
    Little, P. J., Compton, D. R., Johnson, M. R., Melvin, L. S., and Martin, B. R., Pharmacology and stereoselectivity of structurally novel cannabinoids in mice, J. Pharmacol. Exp. Ther., 247, 1046, 1988.PubMedGoogle Scholar
  37. 37.
    Ohlsson, A., Agurell, S., Leander, K., Dahmen, J., Edery, H., Porath, G., Levy, S., and Mechoulam, R., Synthesis and psychotropic activity of side chain hydroxylated delta-6-THC metabolites, Acta Pharm. Suec., 16, 21, 1979.PubMedGoogle Scholar
  38. 38.
    Gaoni, Y. and Mechoulam, R., Isolation, structure and partial synthesis of an active constituent of hashish, J. Am. Chem. Soc., 86, 1646, 1964.CrossRefGoogle Scholar
  39. 39.
    Turner, C. E., Elsohly, M. A., and Boeren, E. G., Constituents of Cannabis sativa L. XVII. A review of the natural constituents, J. Nat. Prod., 43, 169, 1980.PubMedCrossRefGoogle Scholar
  40. 40.
    Gaoni, Y. and Mechoulam, R., Concerning the isomerization of delta-l-to delta-6-tetrahydrocannabinol, J. Anz. Chem. Soc., 88, 5673, 1966.CrossRefGoogle Scholar
  41. 41.
    Mechoulam, R., Ben-Zvi, Z., Varconi, H., and Samuelov, Y., Cannabinoid rearrangements: synthesis of delta-5-tetrahydrocannabinol, Tetrahedron, 29, 1615, 1973.CrossRefGoogle Scholar
  42. 42.
    Srebnik, M., Lander, N., Breuer, A., and Mechoulam, R., Base catalysed double bond isomerizations of cannabinoids: structural and stereochemical aspects., J. Chem. Soc., Perkin Trans. 1, 2881, 1984.Google Scholar
  43. 43.
    Järbe, T. U. C., Hiltunen, A. J., Mechoulam, R., Srebnik, M., and Breuer, A., Separation of the discriminative stimulus effects in stereoisomers of delta-2 and delta3-tetrahydrocannabinols in pigeons, Eur. J. Pharmacol., 156, 361, 1988.CrossRefGoogle Scholar
  44. 44.
    Binder, M., Edery, H., and Porath, G., Delta-7-THC, a noripsychotropic cannabinoid: structure activity considerations in the cannabinoid series, in Marihuana: Biological Effect, Nahas, G. G. and Paton, W. D. M., Eds., Pergamon Press, Oxford, 1979, 71.Google Scholar
  45. 45.
    Wilson, R. S. and May, E. L., 9-Nor-delta-8-THC, a cannabinoid of metabolic interest, J. Med. Chem., 17, 475, 1974.PubMedCrossRefGoogle Scholar
  46. 46.
    Loev, B., Bender, P. E., Dowalo, F., Macko, E., and Fowler, P. J., Cannabinoids. Structure-activity studies, related to 1,2-dimethylheptyl derivatives., J. Med. Chem., 16, 2100, 1973.Google Scholar
  47. 47.
    Korbinits, D. et al., Cannabinoids with an ether side chain. Synthesis, solubilization and analgesic properties, Eur. J. Med. Chem., 20, 492, 1985.Google Scholar
  48. 48.
    Edery, H., Grunfeld, Y., Porath, G., Ben-Zvi, Z., Shani, A., and Mechoulam, R., Structure-activity relationships in the THC series. Modifications on the aromatic ring and on the side chain, Arzneim. Forsch., 22, 1995, 1972.Google Scholar
  49. 49.
    Burstein, S. H., Audette, C. A., Charalambous, A., Doyle, S. A., Guo, Y., Hunter, S. A., and Makriyannis, A., Detection of cannabinoid receptors by photoaffinit labelling, Biochem. Biophys. Res. Commun., 176, 492, 1991.PubMedCrossRefGoogle Scholar
  50. 50.
    Mechoulam, R. and Gaoni Y., The absolute configuration of delta-l-tetrahydrocannabinol, the major active constituent of hashish, Tetrahedron Lett., 1109, 1967.Google Scholar
  51. 51.
    Gaoni, Y. and Mechoulam, R., The isomerization of cannabidiol to tetrahydrocannabinols, Tetrahedron, 22, 1481, 1966.CrossRefGoogle Scholar
  52. 52.
    Mechoulam, R., Lander, N., Varkony, T.-H., Kimmel, I., Becker, O., Ben-Zvi, Z., Edery, H., and Porath, G., Stereochemical requirements for cannabinoid activity, J. Med. Chem., 23, 1068, 1980.PubMedCrossRefGoogle Scholar
  53. 53.
    Mechoulam, R., Devane, W. A., Breuer, A., and Zahalka, J., A random walk through a cannabis field, Pharmacol. Biochem. Behan, 40, 461, 1991.CrossRefGoogle Scholar
  54. 54.
    Wilson, R. S., May, E. L., Martin, B. R., and Dewey, W. L., 9-Nor-9hydroxyhexahydrocannabinols. Synthesis. Some behavioral and analgesic properties and comparison with the tetrahydrocannabinols,. J. Med. Chem., 19, 1165, 1976.PubMedCrossRefGoogle Scholar
  55. 55.
    Mechoulam, R., Braun, P., and Gaoni, Y., Syntheses of delta-1-THC and related cannabinolds. J. Am. Chem. Soc., 94, 6159, 1972.PubMedCrossRefGoogle Scholar
  56. 56.
    Archer, R. A., Stark, P., and Lemberger, L., Nabilone, in Cannabinoids as Therapeutic Agents, Mechoulam, R., Ed., CRC Press, Boca Raton, FL, 1986.Google Scholar
  57. 57.
    Huffman, I W., Joyner, H. H., Lee, M. D., Jordan, R. D., and Pennington, W. T., Synthesis of both enantiomers of nabilone from a common intermediate. Enantiodivergent synthesis of cannabinoids, J. Org . Chem., 56, 2081, 1991.CrossRefGoogle Scholar
  58. 58.
    Harvey, D. J., In vivo metabolism of (+)-trans-delta-9-THC in the mouse, Blomed. Environ. Mass Spectrosc., 16, 117, 1988.CrossRefGoogle Scholar
  59. 59.
    Harvey, D.J. and Marriage, H.J., Metabolism of(+)-trans-delta-8-THC in I the mouse in vitro and in vivo, Drug Metab. Dispos., 15, 914, 1987.PubMedGoogle Scholar
  60. 60.
    Mechoulam, R., Breuer, A., Feigenbaum, J. J., and Devane, W. A., Noripsychotropic synthetic cannabinoids as therapeutic agents, Farmaco,46 (Suppl. 1), 267, 199 1, and unpublished results.Google Scholar
  61. 61.
    Howlett, A. C., Champion, T. M., Wilken, G. H., and Mechoulam, R., Stereochemical effects of 11OH-delta-8-tetrahydrocannabinol-dimethylheptyI to inhibit adenylate cyclase and bind to the cannabinoid receptor, Neuropharrnacology, 29, 161, 1990.CrossRefGoogle Scholar
  62. 62.
    Mechoulam, R., Breuer, A., Järbe, T. U. C., Hiltunen, A. J., and Glaser R., Cannabimimetic activity of novel enantiomeric benzofuran cannabinoids, J. Med. Chem., 33, 1037, 1990.PubMedCrossRefGoogle Scholar
  63. 63.
    Mechoulam, R., The pharmayohistory of Cannabis sativa, in Cannabinoids as Therapeutic Agents, Mechoulam, R., Ed., CRC Press, Boca Raton, FL, 1986.Google Scholar
  64. 64.
    Hollister, L. E., Gillespie, H. K., Mechoulam, R., and Srebnik, M., Human pharmacology of IS and IR enantiomers of delta-3-THC, Psychopharmacology, 92, 505, 1987.PubMedCrossRefGoogle Scholar
  65. 65.
    Consroe, P. and Snider, S. R., Therapeutic potential of cannabinoids in neurological disorders, in Cannabinoids as Therapeutic Agents, Mechoulam, R., Ed., CRC Press, Boca Raton, FL, 1986.Google Scholar
  66. 66.
    Guimaraes, F., Chiaretti, T. M., Graeff, E. G., and Zuardi, A. W., Antianxiety effect of cannabidiol in the elevated plus-maze, Psychophartnacologia, 100, 558, 1990.CrossRefGoogle Scholar
  67. 67.
    Onaivi, E. S., Green, M. R., and Martin, B. R., Pharmacological characterization of cannabinoids in the el I evated plus-maze, J. Phartnacol. Exp. Ther, 252, 1002, 1990.Google Scholar
  68. 68.
    Musty, R. E., Conti, L. H., and Mechoulam, R, Anxiolytic properties of cannabidiol, in Marihuana `84, Harvey, D. J., Ed., IRL Press, Oxford, 1985, 1.Google Scholar
  69. 69.
    Leite, J. R., Carlini, E. A., Lander, N., and Mechoulam, R., Anticonvulsant effect of (-) and (+) isomers of CBD and their dimethyl heptyl hornologq, Pharmacology, 124, 141, 1982.CrossRefGoogle Scholar
  70. 70.
    Nir, I., Ayalon, D., Tsafriri, A., Cordova, T., and Lindner, H. R., Suppression of the cyclic surge of LH secretion and of ovulation in the rat by delta- 1-THC, Nature (Londbn), 243, 470, 1973.CrossRefGoogle Scholar
  71. 71.
    Cordova, T., Ayalon, D., Lander, N., Mechoullam, R., Nir, I., Puder, M., and Lindner, H. R., The ovulation blocking effect of cannabinoids: structure-activity relationships, Psychoneuroendocrinology, 5, 53, 1980.PubMedCrossRefGoogle Scholar
  72. 72.
    Feigenbaum, J. J., Richmond, S. A., Weissman, Y., and Mechoul4m, R., Inhibition of cisplatin induced emesis in the pigeon by a non-psychotropic synthetic cannabinoid, Fur. J. Pharmacol., 169, 159, 1989.Google Scholar
  73. 73.
    Feigenbaum, J. J., Bergmann, F., Richmond, S. A., Mechoulam, R., Nadler, V., Kloog, Y., and Sokolovsky, M., A non-psychotropic cannabinoid acts as a functional N-methyl-D-asparate (NMDA) receplor blocker, Proc. Natl. Acad. Sci, U.S.A., 86, 9584, 1989.CrossRefGoogle Scholar
  74. 74.
    Herkenham, M. et al., Cannabinoid receptor localization in brain, Proc. Nad. Acad. Sci. U.S.A., 87, 1932, 1990.CrossRefGoogle Scholar
  75. 75.
    Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., and Bonner, T. I., Structure of a cannabinoid receptor and functional expression of the cloned cDNA, Nature (London), 346, 561, 1990.CrossRefGoogle Scholar
  76. 76.
    Herkenham, M., Lynn, A. B., Johnson, M. R., Melvin, L. S., de Costa, B. R., and Rice, K. C., Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study,./. Neurosci.. 11, 563, 1991.Google Scholar
  77. 77.
    Howlett, A. C., Johnson, M. R., Melvin, L. S., and Milne, G. M., Nonclassical cannabinoid analgetics inhibit adenylate cyclase: development of a cannabinoid receptor model, Mol. Pharmacol., 33, 297, 1988.PubMedGoogle Scholar
  78. 78.
    Rosenqvist, E. and Ottersen, T., The crystal and molecular structure of delta-9-THC acid B, Acta Chem. Scand. B., 29. 379, 1975.PubMedCrossRefGoogle Scholar
  79. 79.
    Mechoulam, R., Ben-Zvi, Z., Vagnitinsky, B., and Shani, A., A new tetrahydrocannabitiolic acid, Tetrtihedron Lett., 2339, 1969.Google Scholar
  80. 80.
    Archer, R. A., Boyd, D. B., Demarco, P. V., Tyminski, I. J., and Allinger, N. L., Structural studies of cannabinoids. A theoretical and proton magnetic resonance study, J. Am. Chem. Soc., 92, 5200, 1970.Google Scholar
  81. 81.
    Kriwacki, W. and Makriyannis, A., The conformational analysis of delta-9- and delta-9, 11-THCs in solution using high resolution NMR’spectroscopy, Mol. Pharmacol., 35, 495, 1989.PubMedGoogle Scholar
  82. 82.
    Reggio, P. H. and Mazurek, A. P., A molecular reactivity template for cannabinoid activity,./. Mol. Struct., 149, 331, 1987.CrossRefGoogle Scholar
  83. 83.
    Haasnoot, C. A. G., de Leeuw, F. A. A. M., and Altona, C., The relationship between proton-proton NMR coupling constants and substituent elect ronegativ it ies, Tetrahedron, 36, 2783, 1980.CrossRefGoogle Scholar
  84. 84.
    Lambert,J. B. Structural chemistry in solution. The R value, Acct. Chem. Res 4, 87,1971.Google Scholar
  85. 85.
    Hanson, K. R., Applications of the sequence rule. Naming the paired ligands gg at a tetrahedral atom, J. Am. Chem. Soc., 88, 2731, 1966.CrossRefGoogle Scholar
  86. 86.
    Reggio, P. H., Greer, K. V., and Cox, S. M., The importance of the orientation of the C9 substituent to cannabinoid activity, J. Med. Clicni., 32, 1630, 1989.Google Scholar
  87. 87.
    Reggio, P. H., Seltzmann, H. H., Compton, D. R., Prescott, W. R., Jr., and Martin, B. R., Investigation of the role of the phenolic hydroxyl in cannabinoid activity, Mol. Pharmacol., 38, 854. 1990.Google Scholar
  88. 88.
    Semus, S. F. and Martin, B. R., A computergraphic investigation into the pharmacological role of the TFICcannabinoid phenolic moiety, Life Sci., 46, 178 1, 1990.Google Scholar
  89. 89.
    Martin, B. R., Dewey, W. L., Harris, L. S., Bechner, J., Wilson, R. S., and May, E. L., Marihuana-like activity of new synthetic THCs, Pharmacol. Biochem.Behay., 3, 849, 1975.CrossRefGoogle Scholar
  90. 90.
    Munro, S., Thomas, K.L. and Abu-Shaar, M. Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365, 61, 1993.PubMedCrossRefGoogle Scholar
  91. 91.
    Devane, W.A., Hanus, L., Breuer, A., Pertwee, R.G., Stevenson, L.A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A. and Mechoulam, R. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science, 258, 1946, 1992.PubMedCrossRefGoogle Scholar
  92. 92.
    Mechoulam, R., Ben-Shabat, S., Hanus, L., Ligumsky, M., Kaminski, N.E., Schatz, A.R., Gopher, A., Almog, S., Martin, B.R., Compton, D.R., Pertwee, R.G., Griffin, G., Bayewitch, M., Barg, J. and Vogel, Z. Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50, 83, 1995.PubMedCrossRefGoogle Scholar
  93. 93.
    Lagu, S.G., Varona, A., Chambers, J.D. and Reggio, P.H. Construction of a steric map of the binding pocket for cannabinoids at the cannabinoid receptor. Drug Des. Discov. 12, 179, 1995.PubMedGoogle Scholar
  94. 94.
    Bramblett, R.D., Panu, A.M., Ballesteros, J.A. and Reggio P.H. Construction of a 3D model of the cannabinoid CB 1 receptor: determination of helix ends and helix orientation. Life Sci. 56, 1971, 1995.PubMedCrossRefGoogle Scholar
  95. 95.
    Gareau, Y., Dufresne, C., Gallant, M., Rochette, C., Sawyer, N., Slipetz, D.M., Tremblay, N., Weech, P.K., Metters, K.M. and Labelle, M. Structure activity relationships of tetrahydrocannabinol analogues on human cannabinoid receptors. Bioorg. Med. Chem. Lett. 6, 189, 1996.CrossRefGoogle Scholar
  96. 96.
    Rhee, M.-H., Vogel, Z., Barg, J., Bayewitch, M., Levy, R., Hanus, L., Breuer, A. and Mechoulam, R. Canabinol derivative: binding to cannabinoid receptors and inhibition of adenylylcyclase. J. Med. Chem. 40, 3228, 1997.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Raphael Mechoulam
  • W. A. Devane
  • R. Glaser

There are no affiliations available

Personalised recommendations