Various preparations of the plant Cannabis sativa have been used since ancient times for their behavioral and pharmacological properties. R. Mechoulam, The Pharmohistory of Cannabis Sativa, 1-19 (1986). More recently, it has been demonstrated that the active plant constituents, known as cannabinoids, produce a variety of effects including bronchodilation, increased heart rate, reduced intraocular pressure, analgesia, antiemesis, alteration in body temperature, as well as anticonvulsant and psychotropic activities. (W. L. Dewey, Cannabinoid Pharmacology, Pharmacol. Rev., 38:45 (1986)).
Recent evidence supports the hypothesis that cannabinoids also produce some of their effects by interacting with specific protein sites in synaptosomal preparations and mammalian brains. (W. A. Devane et al., "Determination and Characterization of a Cannabinoid Receptor in Rat Brain", Mol. Pharmacol., 34:605-613 (1988); M. Herkenham et al., "Cannabinoid Receptor Localization in Brain", Proc. Natl. Acad. Sci. USA, 87:1932-1936 (1990)). For example, a cannabinoid receptor was shown to be more responsive to the psychoactive cannabinoids than the nonpsychoactive derivatives. (A. C. Howlett, "Cannabinoid Inhibition of Adenylate Cyclase Relative Activity of Constituents and Metabolites of Marihuana", Neuropharmacology, 26:507-512 (1987)). More recently, the cannabinoid receptor was cloned from rat and human cDNA libraries. The cDNA thus obtained when injected in CHO-K.sub.1 cells led to the expression of the cannabinoid G-protein coupled receptor. (L. A. Matsuda, et al., "Structure of a Cannabinoid Receptor and Functional Expression of the Cloned cDNA", Nature, 346:561-564 (1990); C. Gerard et al., "Nucleotide Sequence of Human Cannabinoid Receptor cDNA", Nucleic Acids Res., 18:7142 (1990)). Furthermore, the human cannabinoid receptor gene was shown to be localized to chromosome 6q14-q15. (M. R. Hoehe et al., "Genetics and Physics Mapping of the Human Cannabinoid Receptor Gene to Chromosome 6q14-q15" New Biologist, 3:880-885 (1991)). However, attempts to date to develop affinity labels of probes for the cannabinoid receptor have typically been unsuccessful. Therefore, a need exists to develop compositions which have a good binding affinity for the cannabinoid receptor and thus, can be used as cannabinoid receptor probes.
USPTO Backgrounds
USPTO Backgrounds