Effect of modafinil on pancreatic exocrine secretion in the rat. A comparison with methadone.
Modafinil is a recently developed drug which increases wakefulness in several animal species and in man, an effect involving, at least in part, central adrenoceptors. In the present experiments, the effect of modafinil was studied on a model of neurally stimulated secretion, pancreatic secretion induced by 2-deoxyglucose (2DG) in the rat, and compared with that of the mu-opiate methadone. Modafinil induced a dose-related inhibition of 2DG-stimulated pancreatic secretion, reaching more than 80% after 250 mg/kg i.p. The modafinil effect was suppressed by idazoxan or by large doses of prazosin but not by naloxone. In addition modafinil (250 mg/kg i.p.) did not change the pancreatic response to electrical vagal stimulation. Methadone also potently suppressed 2DG-stimulated pancreatic secretion, but in contrast to modafinil, the methadone effect was blocked by naloxone, but not by the adrenoceptor antagonists idazoxan, prazosin and propranolol. It is concluded that modafinil decreases centrally 2DG-stimulated pancreatic secretion through a pathway involving alpha 1- and alpha 2-adrenoceptors, without an interaction with opiate receptors.
INSERM U 239, Faculté de Médecine Xavier Bichat, Paris, France.
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001559:Benzhydryl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003847:Deoxyglucose / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D008691:Methadone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000077408:Modafinil; D009292:Narcotic Antagonists / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D010525:Peripheral Nerves / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology
D000317:Adrenergic alpha-Antagonists; D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D003847:Deoxyglucose; D000077408:Modafinil; D008691:Methadone