Use of a potential rabbit model for structure-behavioral activity studies of cannabinoids

Consroe, Paul; Martin, Arnold R.; Fish, Barbara Schneiderman

doi:10.1021/jm00347a021

Cited by 20 publications

(8 citation statements)

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“…In rats, low doses of Ay-THC and 11 -OH-A9-THC evoke focal cortical epileptic bursts in a dose-dependent fashion, but cannabidiol has no effect even at high doses (Turkanis and Karler, 1982). In one rabbit strain, cannabinoids elicit convulsions at low doses and with relative potencies predicted by the structure-activity relationship (Consroe et al, 1982).…”

Section: Discussionmentioning

confidence: 98%

Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study

et al. 1991

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A potent, synthetic cannabinoid was radiolabeled and used to characterize and precisely localize cannabinoid receptors in slide-mounted sections of rat brain and pituitary. Assay conditions for 3H-CP55,940 binding in Tris-HCl buffer with 5% BSA were optimized, association and dissociation rate constants determined, and the equilibrium dissociation constant (Kd) calculated (21 nM by liquid scintillation counting, 5.2 nM by quantitative autoradiography). The results of competition studies, using several synthetic cannabinoids, add to prior data showing enantioselectivity of binding and correlation of in vitro potencies with potencies in biological assays of cannabinoid actions. Inhibition of binding by guanine nucleotides was selective and profound: Nonhydrolyzable analogs of GTP and GDP inhibited binding by greater than 90%, and GMP and the nonhydrolyzable ATP analog showed no inhibition. Autoradiography showed great heterogeneity of binding in patterns of labeling that closely conform to cytoarchitectural and functional domains. Very dense 3H-CP55,940 binding is localized to the basal ganglia (lateral caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra pars reticulata), cerebellar molecular layer, innermost layers of the olfactory bulb, and portions of the hippocampal formation (CA3 and dentate gyrus molecular layer). Moderately dense binding is found throughout the remaining forebrain. Sparse binding characterizes the brain stem and spinal cord. Densitometry confirmed the quantitative heterogeneity of cannabinoid receptors (10 nM 3H-CP55,940 binding ranged in density from 6.3 pmol/mg protein in the substantia nigra pars reticulata to 0.15 pmol/mg protein in the anterior lobe of the pituitary). The results suggest that the presently characterized cannabinoid receptor mediates physiological and behavioral effects of natural and synthetic cannabinoids, because it is strongly coupled to guanine nucleotide regulatory proteins and is discretely localized to cortical, basal ganglia, and cerebellar structures involved with cognition and movement.

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Section: Discussionmentioning

confidence: 98%

Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study

et al. 1991

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“…Extensive reviews of these results are found elsewhere (Dewey, 1986;Razdan, 1986). Pharmacological effects have been meastired with models such as dog ataxia (Loewe, 1947), the THC-seizure susceptible rabbit (Consroe et al, 1982), monkey overt behavior (Grunfeld & Edery, 1969;Edery et al, 1971;Edery et al, 1972), drug discrimination (Balster & Prescott, 1992) and a mouse behavioral battery consisting of spontaneous locomotor activity, hypothermia, immobility (catalepsy) and antinociception (Martin, 1985). Although cannabinoids have direct cellular actions on peripheral tissues, most of the behavioral and pharmacological effects studied by researchers appear to involve the central nervous system (Dewey, 1986).…”

Section: Animal Models and Pharmacologymentioning

confidence: 99%

Cannabis: pharmacology and toxicology in animals and humans

Adams¹,

Martin²

1996

Addiction

367

174

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Cannabis is one of the most widely used drugs throughout the world. The psychoactive constituent of cannabis, delta 9-tetrahydrocannabinol (delta 9-THC), produces a myriad of pharmacological effects in animals and humans. For many decades, the mechanism of action of cannabinoids, compounds which are structurally similar to delta 9-THC, was unknown. Tremendous progress has been made recently in characterizing cannabinoid receptors both centrally and peripherally and in studying the role of second messenger systems at the cellular level. Furthermore, an endogenous ligand, anandamide, for the cannabinoid receptor has been identified. Anandamide is a fatty-acid derived compound that possesses pharmacological properties similar to delta 9-THC. The production of complex behavioral events by cannabinoids is probably mediated by specific cannabinoid receptors and interactions with other neurochemical systems. Cannabis also has great therapeutic potential and has been used for centuries for medicinal purposes. However, cannabinoid-derived drugs on the market today lack specificity and produce many unpleasant side effects, thus limiting therapeutic usefulness. The advent of highly potent analogs and a specific antagonist may make possible the development of compounds that lack undesirable side effects. The advancements in the field of cannabinoid pharmacology should facilitate our understanding of the physiological role of endogenous cannabinoids.

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“…Although neither these nor any other pairs of optically pure THC stereoisomers have been evaluated for anticonvulsant or ROT neurotoxicity effects, the comparative activities (or in some cases, dose-response potencies) of the enantiomers of delta-1-THC and of delta-6-THC (Consroe et al 1982;Dewey et al 1984) have been ascertained in several other laboratory animal paradigms.…”

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confidence: 99%

Structure-Activity Relationships of Tricyclic and Nonclassical Bicyclic Cannabinoids

Mr²

1987

PsycEXTRA Dataset

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The Research Analysis and Utilization System (RAUS) is designed to serve four functions: Collect and systematically classify the findings of all intramural and extramural research supported by the National Institute on Drug Abuse (NIDA); Evaluate the findings in selected areas of particular interest and formulate a state-of-the-art review by a panel of scientific peers; Disseminate findings to researchers in the field and to administrators, planners, instructors, and other interested persons; Provide a feedback mechanism to NIDA staff and planners so that the administration and monitoring of the NIDA research program reflect the very latest knowledge gleaned from research in the field. Since the number of research topics that can be intensively reviewed annually is limited, four subject areas are chosen each year to undergo a thorough examination. Distinguished scientists are invited to participate. Each scientist is provided reports from NIDA-funded research and asked to add information derived from the literature and his or her own research and to prepare a comprehensive, state-of-the-art review paper on an assigned topic. These papers, together with a summary of the discussions which take place at the review meeting, make up a RAUS Review Report in the NIDA Research Monograph series. In recent years a large number of reviews and books have appeared summarizing research advances in the chemistry, pharmacology, toxicology, metabolism, and distribution of cannabinoids and their synthetic analogs. Yet the volume of research on structure-activity relationships of cannabinoids appears to have decreased. In order to evaluate NIDA's current research program on cannabinoids, to rekindle interest in this critical area, and to focus attention on profitable avenues for future research, NIDA found it timely to bring together experts on the structure-activity relationships of cannabinoids for a comprehensive review. v

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Use of a potential rabbit model for structure-behavioral activity studies of cannabinoids

Cited by 20 publications

References 9 publications

Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study

Characterization and localization of cannabinoid receptors in rat brain: a quantitative in vitro autoradiographic study

Cannabis: pharmacology and toxicology in animals and humans

Structure-Activity Relationships of Tricyclic and Nonclassical Bicyclic Cannabinoids

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