Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D05731 (Rimonabant)
 326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent studies suggest that blockade of cannabinoid CB1 receptors suppresses feeding, an effect observed in humans treated with the cannabinoid CB1 antagonist Rimonabant. A cross-talk between cannabinoids and other systems controlling appetite might exist since cannabinoid receptors are present in hypothalamic neural circuits involved in feeding regulation and energy expenditure. Orexin A-hypocretin 1, an orexigenic peptide, is an ideal candidate to interact with cannabinoid receptors. Both of them play an important role in feeding and they co-localize in similar brain regions. To study this hypothesis we investigated (a) the effects on food intake of either orexin A-hypocretin 1 or the cannabinoid CB1 receptor antagonist Rimonabant in pre-fed rats, and (b) the interaction between them by monitoring the effects of the combined administration of cannabinoids and orexin A-hypocretin 1 in pre-fed rats. The results show that (1) orexin A-hypocretin 1 is a short-term modulator of appetite that increases food intake in pre-fed rats, (2) Rimonabant decreases food intake and (3) such effective and subeffective doses of Rimonabant block the orexigenic effect of orexin A-hypocretin 1. The results support the idea that cannabinoid and orexin A-hypocretin 1 systems share a common mechanism in food intake and indicate that the hypothalamic orexigenic circuits are involved in cannabinoid CB1 receptor antagonism-mediated reduction of appetite.
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PMID:Pretreatment with subeffective doses of Rimonabant attenuates orexigenic actions of orexin A-hypocretin 1. 1788 9

Numerous studies have demonstrated that administration of rimonabant (SR 141716), a CB(1) receptor antagonist, causes a decrease in energy intake. However, the mechanisms by which rimonabant exerts its anorectic actions are unclear. The main focus of the study reported here was to establish the chemical identity of neurons that may subserve the anorectic effects of rimonabant. As such three approaches were utilised: (i) the identification of rimonabant-activated neurons using Fos as a marker of neuronal activity; (ii) the identification of the chemical phenotype of rimonabant-activated neurons by combining immunocytochemical identification of Fos and feeding-related peptides; and (iii) the evaluation of the effect of rimonabant on messenger RNA (mRNA) and protein for a number of feeding-related peptides. Rimonabant-induced Fos-positive nuclei were localized within a range of discrete hypothalamic regions with a predominance in the parvocellular part of the paraventricular nucleus of the hypothalamus, dorsomedial hypothalamus, arcuate nucleus and lateral hypothalamic area. Furthermore, Fos labelling within these hypothalamic regions was colocalized with anorexigenic and orexigenic peptides including melanin-concentrating hormone (MCH), orexin, cocaine- and amphetamine-regulated transcript (CART) and alpha-melanocyte-stimulating hormone (alpha-MSH). Rimonabant specifically induced a decrease in NPY and an increase in CART and alpha-MSH mRNA and protein, consistent with its effect in reducing food intake and increasing energy expenditure. As such these data provide insights into the mechanisms of action that may underpin rimonabant's effects on energy balance and body weight.
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PMID:Involvement of hypothalamic peptides in the anorectic action of the CB receptor antagonist rimonabant (SR 141716). 1949 94