Inhibition of THC-induced effects on the central nervous system and heart rate by a novel CB1 receptor antagonist AVE1625.
CB1 antagonists such as AVE1625 are potentially useful in the treatment of obesity, smoking cessation and cognitive impairment. Proof of pharmacological action of AVE1625 in the brain can be given by antagonising the effects of delta-9-tetrahydrocannabinol (THC), a CB1/CB2 agonist. Inhibition of THC-induced effects by AVE1625 was observed on Visual Analogue Scales 'alertness', 'feeling high', 'external perception', 'body sway' and 'heart rate'. Even the lowest dose of AVE1625 20 mg inhibited most of THC-induced effects. AVE1625 did not have any effect on psychological and behavioural parameters or heart rate by itself. After THC and AVE1625 administration, changes on electroencephalography were observed. This study shows a useful method for studying the effects of CB1 antagonists. AVE1625 penetrates the brain and antagonises THC-induced effects with doses at or above 20 mg.
Zuurman
L
L
Centre for Human Drug Research, Leiden, The Netherlands. linekezuurman@gmail.com
Roy
C
C
Schoemaker
R C
RC
Amatsaleh
A
A
Guimaeres
L
L
Pinquier
J L
JL
Cohen
A F
AF
van Gerven
J M A
JM
D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D002490:Central Nervous System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004347:Drug Interactions; D004569:Electroencephalography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D004856:Postural Balance / Q000187:drug effects; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology*
C523652:AVE1625; D006846:Hydrocarbons, Halogenated; D043884:Receptor, Cannabinoid, CB1; D013449:Sulfonamides; D013759:Dronabinol