| Autor: |
Järbe TU; Department of Psychology, Temple University, Philadelphia, Pennsylvania, USA. t.jarbe@neu.edu, Deng H, Vadivel SK, Makriyannis A |
| Jazyk: |
angličtina |
| Zdroj: |
Behavioural pharmacology [Behav Pharmacol] 2011 Sep; Vol. 22 (5-6), pp. 498-507. |
| DOI: |
10.1097/FBP.0b013e328349fbd5 |
| Abstrakt: |
We examined four different cannabinergic aminoalkylindole ligands, including one drug (AM678=JWH018) found in herbal 'Spice' concoctions, for their ability to substitute for Δ(9)-tetrahydrocannabinol (THC), and the ability of the cannabinoid receptor 1-selective antagonist/inverse agonist rimonabant to block the substitution, 30 and 90 min after intraperitoneal injection. Rats trained to discriminate the effects of vehicle from those produced by 3 mg/kg of THC were used. The order of potency was: AM5983≥AM678>AM2233>WIN55212-2 at both test intervals. AM5983 and AM678 appeared eight times more potent than THC, followed by AM2233 (about twice as potent as THC), and WIN55212-2 approximately THC at the 30-min test interval. The aminoalkylindoles showed reduced potency (i.e. an increased ED50 value) at the longer injection-to-test interval of 90 min compared with testing at 30 min. The rightward shifts by coadministration of rimonabant were approximately 8-fold to 12-fold for AM5983 and AM678, compared with an approximately 3-fold rightward shift for the WIN55212-2 curve. AM2233 (1.8 mg/kg) substitution was also blocked by 1 mg/kg of rimonabant. In conclusion, AM5983 and AM678=JWH018 are potent cannabimimetics derived from an aminoalkylindole template. WIN55212-2 seemed to interact differently with rimonabant, compared with either AM5983 or AM678, indicating potential differences in the mechanism(s) of action among cannabinergic aminoalkylindoles. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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