SR147778 [5-(4-bromophenyl)-1-(2,4-dichlorophenyl)-4-ethyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide], a new potent and selective antagonist of the CB1 cannabinoid receptor: biochemical and pharmacological characterization.

Based on binding, functional, and pharmacological data, this study introduces SR147778 [5-(4-bromophenyl)-1-(2,4-dichloro-phenyl)-4-ethyl-N-(1-piperidinyl)-1H-pyrazole-3-carboxamide] as a highly potent, selective, and orally active antagonist for the CB1 receptor. This compound displays nanomolar affinity (Ki = 0.56 and 3.

Activity of SR141716 on post-reinforcement pauses in operant responding for sucrose reward in rats.

Cannabinoids increase food intake, via CB1 receptors. The CB1 antagonist, SR141716, has been reported to decrease palatable food consumption in both operant and non-operant procedures. Similarly, CB1 receptor blockade diminished responding for normal food pellets under a fixed-ratio 15 (FR-15) schedule of reinforcement.

Improvement of memory in rodents by the selective CB1 cannabinoid receptor antagonist, SR 141716.

Social short-term memory in rodents is based on the recognition of a juvenile by an adult conspecific when the juvenile is presented on two successive occasions. Cannabimimetics are claimed to induce memory deficits in both humans and animals. In the brain, they mainly bind to CB1 receptors for which anandamide is a purported endogenous ligand.

Central mediation of the cannabinoid cue: activity of a selective CB1 antagonist, SR 141716A.

Active cannabimimetic drugs are known to bind to two receptor subtypes: one, called CB1, is mainly localised in the central nervous system while the other (CB2) is expressed preferentially in the immune system. SR 141716A has been demonstrated to have a nanomolar affinity for CB1 receptor subtypes and a micromolar affinity for CB2 receptors. Moreover, it is an effective antagonist at these receptors both in vitro (antagonism of cannabinoid activity in vas deferens) and in vivo (suppression of the hypothermia elicited by WIN 55,212-2).

Antidepressant-like effects of SR 57227A, a 5-HT3 receptor agonist, in rodents.

We have investigated the effect of SR 57227A, a selective 5-HT3 receptor agonist which crosses the blood brain barrier, on three rodent models in which antidepressants are active. In the forced swimming test, SR 57227A dose-dependently reduced the duration of immobility in mice and rats after i.p.