Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presatiated adult male Lister hooded rats received oral administration of the exogenous cannabinoid Delta-9-tetrahydrocannabinol (Delta(9)-THC; 1.0 mg/kg) in combination with subcutaneous injection of either the cannabinoid CB1 antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716; 0, 0.05, 0.1, 0.5 or 1.0 mg/kg), the CB2 antagonist N-[(1S)-endo-1,3,3-trimethyl bicyclo[2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528; 0, 0.05, 0.1, 0.5 or 1.0 mg/kg), the general opioid antagonist naloxone (0.1, 0.5, 1.0 or 5.0 mg/kg) or the 5-HT agonist dexfenfluramine (0.05, 0.1, 0.5, 1.0 or 5.0 mg/kg). Food (chow) intake was measured over 2 h from the onset of the dark period. Delta(9)-THC induced significant hyperphagia, which was attenuated by subanorectic doses of SR141716 and naloxone. Neither SR144528 nor dexfenfluramine affected Delta(9)-THC-induced feeding. These data confirm mediation of Delta(9)-THC hyperphagia by central-type CB1 receptors, and support a functional relationship between cannabinoid and opioid systems in relation to appetite regulation. Stimulation of CB1 receptors may promote feeding by actions on food reward rather than by inhibition of serotonergic satiety mechanisms.
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PMID:Reversal of delta 9-THC hyperphagia by SR141716 and naloxone but not dexfenfluramine. 1181 41

Recent studies suggest that the endocannabinoid system modulates feeding. Despite the existence of central mechanisms for the regulation of food intake by endocannabinoids, evidence indicates that peripheral mechanisms may also exist. To test this hypothesis, we investigated (1) the effects of feeding on intestinal anandamide accumulation; (2) the effects of central (intracerebroventricular) and peripheral (intraperitoneal) administration of the endocannabinoid agonist anandamide, the synthetic cannabinoid agonist R-(+)-(2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrol[1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl) methanone monomethanesulfonate (WIN55,212-2), and the CB1-selective antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide (SR141716A) on food intake in rats; and (3) the effects of sensory deafferentation on the modulation of feeding by cannabinoids. Food deprivation produced a sevenfold increase in anandamide content in the small intestine but not in the brain or stomach. Refeeding normalized intestinal anandamide levels. Peripheral but not central administration of anandamide or WIN55,212-2 promoted hyperphagia in partially satiated rats. Similarly, peripheral but not central administration of SR141716A reduced food intake. Capsaicin deafferentation abolished the peripheral effects of both cannabinoid agonists and antagonists, suggesting that these agents modulate food intake by acting on CB1 receptors located on capsaicin-sensitive sensory terminals. Oleoylethanolamide, a noncannabinoid fatty ethanolamide that acts peripherally, prevented hyperphagia induced by the endogenous cannabinoid anandamide. Pretreatment with SR141716A enhanced the inhibition of feeding induced by intraperitoneal administration of oleoylethanolamide. The results reveal an unexpected role for peripheral CB1 receptors in the regulation of feeding.
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PMID:A peripheral mechanism for CB1 cannabinoid receptor-dependent modulation of feeding. 1241 86

We determined the effect of a cannabinoid CB1 receptor antagonist (AM-251; N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) on food intake, body weight and adipose tissue mass in Western diet-induced obese (DIO) mice using a chronic, interrupted, oral dosing paradigm. The dosing paradigm was 2 weeks on treatment (treatment 1), 2 weeks off-treatment, followed by 2 weeks on treatment (treatment 2). During treatment 1 and treatment 2, food intake and body weight were reduced after a single dose. At 30 mg/kg/day, anorectic efficacy was maintained through 12 days (treatment 1) and 7 days (treatment 2). Body weight of AM-251-treated mice remained less than vehicle-treated mice throughout treatment 1 and treatment 2. Administration of AM-251 reduced inguinal subcutaneous, retroperitoneal and mesenteric adipose tissue mass. Antiobesity effects of AM-251 were lost during the off-treatment period, and hyperphagia was observed in treated animals. With re-initiation of AM-251 treatment, mice again responded to the effects of the compound. These results support the hypothesis that chronic treatment of obese individuals with cannabinoid CB1 receptor antagonists is a viable pharmacologic approach to sustained weight loss.
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PMID:Antiobesity effects of chronic cannabinoid CB1 receptor antagonist treatment in diet-induced obese mice. 1259 Nov 4

Recent research suggests that cannabinoid CB1 receptor antagonism reduces appetite and body weight gain. The present study was designed to assess the sub-chronic effects of the selective cannabinoid CB1 receptor antagonist, AM251 (N-(Piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide), in young ob/ob mice. Pair-fed animals were used as additional controls. Daily injection of AM251 (6 mg/kg body weight) for 18 days significantly (P<0.05) decreased daily and 18-day cumulative food intake. The corresponding body weight change did not achieve significance and values were not different from pair-fed mice. Non-fasting plasma glucose was decreased (P<0.05) from day 10 onwards by AM251 treatment. The glycaemic response to intraperitoneal glucose was correspondingly improved (P<0.05) in AM251 treated mice. In keeping with this, insulin sensitivity was enhanced (P<0.05) compared to controls. Furthermore, adipose mRNA levels of acetyl-CoA carboxylase 1 were significantly (P<0.05) reduced by 18 days AM251 treatment. There were no differences in either non-fasting or glucose-stimulated insulin release. Pair-feeding had broadly similar metabolic effects to AM251 treatment apart from increased (P<0.01) locomotor activity which was only observed in AM251 treated ob/ob mice. These data indicate that sub-chronic antagonism of the cannabinoid CB1 receptor by daily treatment with AM251 counters aspects of the hyperphagia-related impairment of ob/ob mouse metabolism. Such effects seem predominantly mediated by restriction of energy intake.
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PMID:Antidiabetic effects of sub-chronic administration of the cannabinoid receptor (CB1) antagonist, AM251, in obese diabetic (ob/ob) mice. 1819 Nov 22

The cannabinoid receptor 1 (CB(1)R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB(1)R that regulate these physiological functions are unknown. CB(1)R is widely expressed, including in neurons of the parasympathetic branches of the autonomic nervous system. The vagus nerve has been implicated in the regulation of several aspects of metabolism and energy balance (e.g., food intake and glucose balance), and gastrointestinal functions including motility. To directly test the relevance of CB(1)R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB(1)R in afferent and efferent branches of the vagus nerve (Cnr1(flox/flox); Phox2b-Cre mice). On a chow or on a high-fat diet, Cnr1(flox/flox); Phox2b-Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1(flox/flox) control mice. Also, fasting-induced hyperphagia and after acute or chronic pharmacological treatment with SR141716 [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole carboxamide] (CB(1)R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1(flox/flox); Phox2b-Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB(1)R in the vagus nerve as a key component underlying normal gastrointestinal motility.
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PMID:Cannabinoid receptor 1 in the vagus nerve is dispensable for body weight homeostasis but required for normal gastrointestinal motility. 2283 66