In the present work, the characterization of the biotransformation and bioactivation pathways of the cannabinoid receptor 1 antagonist rimonabant (Acomplia) is described. Rimonabant was approved in Europe in 2006 for the treatment of obesity but was withdrawn in 2008 because of a significant drug-related risk of serious psychiatric disorders. The aim of the present work is to characterize the b...

Effects of the cannabinoid antagonist rimonabant on the EEG were investigated in healthy, non-epileptic rats. The drug was administered orally at 30 mg/kg/day for 3 weeks. The EEG was recorded continuously. In 3 out of 13 rats, limbic convulsive seizures, which were not related to the time of drug administration, were observed after 5-8 days. We hypothesize that an accumulation of micro-injurie...

Several cannabinoids elicit systemic vasodilation, mainly via CB1 cannabinoid and vanilloid receptors. However, effects in the pulmonary circulation are unknown. Using the isolated, ventilated, buffer-perfused rabbit lung, we have shown that the endocannabinoids arachidonyl ethanolamide (anandamide) and 2-arachidonyl glycerol (2-AG) dose-dependently increase pulmonary arterial pressure (+19.9 +...

INTRODUCTION Anxiety is among the most common and treatable mental disorders. Adrenergic and cannabinoid systems have an important role in the neurobiology of anxiety. The elevated plus-maze (EPM) has broadly been used to investigate anxiolytic and anxiogenic compounds. The present study investigated the effects of intraperitoneal (IP) injection of cannabinoid CB1 receptor antagonist (AM251) in...

Synthetic cannabinoids (SC) are a heterogeneous group of substances with a high affinity for cannabinoid receptors. Unlike Δ9-tetrahydrocannabinol (THC), synthetic cannabinoids are incredibly potent, highly productive, have more affinity for the Cannabinoid receptor type 1 (CB1), and Cannabinoid receptor type 2 (CB2), and are designed to accelerate the effects of tetrahydrocannabinol. Also, the...

GW405833, widely accepted as a cannabinoid receptor 2 (CB2) agonist, suppresses pathologic pain in preclinical models without the unwanted central side effects of cannabinoid receptor 1 (CB1) agonists; however, recent in vitro studies have suggested that GW405833 may also behave as a noncompetitive CB1 antagonist, suggesting that its pharmacology is more complex than initially appreciated. Here...

Preclinical and clinical research shows that the cannabinoid brain receptor type 1 (CB(1)) modulates alcohol- and nicotine-related behaviors. Throughout the nicotine-induced relapse to alcohol, the rats were pre-treated for 10 days with the CB(1) cannabinoid receptor antagonist rimonabant (0, 0.03, 0.3 and 3.0 mg/kg i.p.). In this condition, a long-lasting nicotine-induced relapse to alcohol wa...

Drug dependence is a chronic relapsing brain disorder characterized by neurobiological changes that lead to a compulsion to take a drug with loss of control over drug intake. Abused drugs (cannabinoids, opioids, ethanol, nicotine and psychostimulants) by interacting with various neural pathways in brain induces pleasant state and responsible for relapses. All abused drugs have common property o...

Recent studies have shown that the endocannabinoid system is involved in the common neurobiological mechanism underlying drug addiction. This system participates in the primary rewarding effects of cannabinoids, nicotine, alcohol and opioids, through the release of endocannabinoids in the ventral tegmental area. Endocannabinoids are also involved in the motivation to seek drugs by a dopamine-in...

AIM To study the potential role of dependence status on CB1-mediated blockade of ethanol self-administration. METHODS We examined the effects of the cannabinoid antagonist SR141716A (0, 0.03, 0.3, and 3 mg/kg) on operant ethanol (10% v/v) self-administration in male Wistar rats that were made ethanol-dependent by chronic (14 d) exposure to ethanol vapor-chambers or exposed to air in identical...