| Abstrakt: |
We examined four different cannabinergic aminoalkylindole ligands, including one drug (AM678=JWH018) found in herbal ‘Spice’ concoctions, for their ability to substitute for 9-tetrahydrocannabinol (THC), and the ability of the cannabinoid receptor 1-selective antagonistinverse 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 mgkg 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 ED50value) 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 mgkg) substitution was also blocked by 1 mgkg 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. |
