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(+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only.
Eur J Pharmacol. 2004 Dec 15; 506(2):179-88.EJ

Abstract

Delta9-Tetrahydrocannabinol (Delta9-THC) and (-)-cannabidiol are major constituents of the Cannabis sativa plant with different pharmacological profiles: (-)-Delta9-tetrahydrocannabinol, but not (-)-cannabidiol, activates cannabinoid CB1 and CB2 receptors and induces psychoactive and peripheral effects. We have tested a series of (+)-cannabidiol derivatives, namely, (+)-cannabidiol-DMH (DMH-1,1-dimethylheptyl-), (+)-7-OH-cannabidiol-DMH, (+)-7-OH- cannabidiol, (+)-7-COOH- cannabidiol and (+)-7-COOH-cannabidiol-DMH, for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice. Although all (+)-cannabidiols bind to cannabinoid CB1 and CB2 receptors, only (+)-7-OH-cannabidiol-DMH was centrally active, while all (+)-cannabidiol analogues completely arrested defecation. The effects of (+)-cannabidiol-DMH and (+)-7-OH-cannabidiol-DMH were partially antagonized by the cannabinoid CB1 receptor antagonist N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716), but not by the cannabinoid CB2 receptor antagonist N-[-(1S)-endo-1,3,3-trimethil bicyclo [2.2.1] heptan-2-yl-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), and had no effect on CB1(-/-) receptor knockout mice. (+)-Cannabidiol-DMH inhibited the peripheral pain response and arachidonic-acid-induced inflammation of the ear. We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions.

Authors+Show Affiliations

Department of Behavioral Sciences, College of Judea and Samaria, Ariel 44837, Israel. fride@research.yosh.ac.ilNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15588739

Citation

Fride, Ester, et al. "(+)-Cannabidiol Analogues Which Bind Cannabinoid Receptors but Exert Peripheral Activity Only." European Journal of Pharmacology, vol. 506, no. 2, 2004, pp. 179-88.
Fride E, Feigin C, Ponde DE, et al. (+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only. Eur J Pharmacol. 2004;506(2):179-88.
Fride, E., Feigin, C., Ponde, D. E., Breuer, A., Hanus, L., Arshavsky, N., & Mechoulam, R. (2004). (+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only. European Journal of Pharmacology, 506(2), 179-88.
Fride E, et al. (+)-Cannabidiol Analogues Which Bind Cannabinoid Receptors but Exert Peripheral Activity Only. Eur J Pharmacol. 2004 Dec 15;506(2):179-88. PubMed PMID: 15588739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - (+)-Cannabidiol analogues which bind cannabinoid receptors but exert peripheral activity only. AU - Fride,Ester, AU - Feigin,Cfir, AU - Ponde,Datta E, AU - Breuer,Aviva, AU - Hanus,Lumír, AU - Arshavsky,Nina, AU - Mechoulam,Raphael, PY - 2004/08/18/received PY - 2004/10/18/revised PY - 2004/10/20/accepted PY - 2004/12/14/pubmed PY - 2005/5/7/medline PY - 2004/12/14/entrez SP - 179 EP - 88 JF - European journal of pharmacology JO - Eur J Pharmacol VL - 506 IS - 2 N2 - Delta9-Tetrahydrocannabinol (Delta9-THC) and (-)-cannabidiol are major constituents of the Cannabis sativa plant with different pharmacological profiles: (-)-Delta9-tetrahydrocannabinol, but not (-)-cannabidiol, activates cannabinoid CB1 and CB2 receptors and induces psychoactive and peripheral effects. We have tested a series of (+)-cannabidiol derivatives, namely, (+)-cannabidiol-DMH (DMH-1,1-dimethylheptyl-), (+)-7-OH-cannabidiol-DMH, (+)-7-OH- cannabidiol, (+)-7-COOH- cannabidiol and (+)-7-COOH-cannabidiol-DMH, for central and peripheral (intestinal, antiinflammatory and peripheral pain) effects in mice. Although all (+)-cannabidiols bind to cannabinoid CB1 and CB2 receptors, only (+)-7-OH-cannabidiol-DMH was centrally active, while all (+)-cannabidiol analogues completely arrested defecation. The effects of (+)-cannabidiol-DMH and (+)-7-OH-cannabidiol-DMH were partially antagonized by the cannabinoid CB1 receptor antagonist N-(piperidiny-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716), but not by the cannabinoid CB2 receptor antagonist N-[-(1S)-endo-1,3,3-trimethil bicyclo [2.2.1] heptan-2-yl-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), and had no effect on CB1(-/-) receptor knockout mice. (+)-Cannabidiol-DMH inhibited the peripheral pain response and arachidonic-acid-induced inflammation of the ear. We conclude that centrally inactive (+)-cannabidiol analogues should be further developed as antidiarrheal, antiinflammatory and analgesic drugs for gastrointestinal and other peripheral conditions. SN - 0014-2999 UR - https://www.unboundmedicine.com/medline/citation/15588739/_+__Cannabidiol_analogues_which_bind_cannabinoid_receptors_but_exert_peripheral_activity_only_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-2999(04)01234-8 DB - PRIME DP - Unbound Medicine ER -