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(-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats.
Behav Pharmacol. 2004 Nov; 15(7):517-21.BP

Abstract

(-)-Adamantyl-Delta8-tetrahydrocannabinol (AM-411) is a 'classical' tricyclic cannabinoid CB1 receptor agonist in which the C-3 alkyl side-chain has been replaced with an adamantyl group. The compound is cannabinoid CB1 receptor subtype selective (CB1 Ki=6.86 nmol/l, CB2 Ki=52.0 nmol/l). We examined the effects of AM-411 alone and in combination with the cannabinoid CB1 receptor antagonist/inverse agonist, SR-141716, on open-field behaviors of rats. The lowest effective dose of AM-411, 3 mg/kg, suppressed ambulation (horizontal activity) and rearing (vertical activity) and increased circling frequency compared to vehicle control levels. Co-administration of SR-141716 normalized these changes. SR-141716 (3 and 5.6 mg/kg) also produced significant increases in scratching and grooming (both frequency and duration), effects that were not eliminated in the presence of AM-411. Coupled with previous drug discrimination data, the open-field profile of AM-411 suggests that this high-affinity CB1 cannabinoid receptor agonist induces behavioral effects similar to the natural cannabinoid Delta9-tetrahydrocannabinol and different from (R)-methanandamide, a chiral analog of the endogenous ligand anandamide.

Authors+Show Affiliations

Temple University, Department of Psychology, Philadelphia, Pennsylvania 19122, USA. tjarbe@astro.temple.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15472574

Citation

Järbe, T U C., et al. "(-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a Selective Cannabinoid CB1 Receptor Agonist: Effects On Open-field Behaviors and Antagonism By SR-141716 in Rats." Behavioural Pharmacology, vol. 15, no. 7, 2004, pp. 517-21.
Järbe TU, DiPatrizio NV, Lu D, et al. (-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats. Behav Pharmacol. 2004;15(7):517-21.
Järbe, T. U., DiPatrizio, N. V., Lu, D., & Makriyannis, A. (2004). (-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats. Behavioural Pharmacology, 15(7), 517-21.
Järbe TU, et al. (-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a Selective Cannabinoid CB1 Receptor Agonist: Effects On Open-field Behaviors and Antagonism By SR-141716 in Rats. Behav Pharmacol. 2004;15(7):517-21. PubMed PMID: 15472574.
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TY - JOUR T1 - (-)-Adamantyl-delta8-tetrahydrocannabinol (AM-411), a selective cannabinoid CB1 receptor agonist: effects on open-field behaviors and antagonism by SR-141716 in rats. AU - Järbe,T U C, AU - DiPatrizio,N V, AU - Lu,D, AU - Makriyannis,A, PY - 2004/10/9/pubmed PY - 2005/2/18/medline PY - 2004/10/9/entrez SP - 517 EP - 21 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 15 IS - 7 N2 - (-)-Adamantyl-Delta8-tetrahydrocannabinol (AM-411) is a 'classical' tricyclic cannabinoid CB1 receptor agonist in which the C-3 alkyl side-chain has been replaced with an adamantyl group. The compound is cannabinoid CB1 receptor subtype selective (CB1 Ki=6.86 nmol/l, CB2 Ki=52.0 nmol/l). We examined the effects of AM-411 alone and in combination with the cannabinoid CB1 receptor antagonist/inverse agonist, SR-141716, on open-field behaviors of rats. The lowest effective dose of AM-411, 3 mg/kg, suppressed ambulation (horizontal activity) and rearing (vertical activity) and increased circling frequency compared to vehicle control levels. Co-administration of SR-141716 normalized these changes. SR-141716 (3 and 5.6 mg/kg) also produced significant increases in scratching and grooming (both frequency and duration), effects that were not eliminated in the presence of AM-411. Coupled with previous drug discrimination data, the open-field profile of AM-411 suggests that this high-affinity CB1 cannabinoid receptor agonist induces behavioral effects similar to the natural cannabinoid Delta9-tetrahydrocannabinol and different from (R)-methanandamide, a chiral analog of the endogenous ligand anandamide. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/15472574/____Adamantyl_delta8_tetrahydrocannabinol__AM_411__a_selective_cannabinoid_CB1_receptor_agonist:_effects_on_open_field_behaviors_and_antagonism_by_SR_141716_in_rats_ L2 - https://doi.org/10.1097/00008877-200411000-00008 DB - PRIME DP - Unbound Medicine ER -