p-Chloroamphetamine, a serotonin-releasing drug, elicited in rats a hyperglycemia mediated by the 5-HT1A and 5-HT2B/2C receptors.
The effects of a serotonin (5-HT) releasing drug, p-chloroamphetamine, on plasma glucose levels were investigated in rats. p-Chloroamphetamine elicited a significant hyperglycemia. The hyperglycemic effects of p-chloroamphetamine were completely prevented by the 5-HT synthesis inhibitor, p-chlorophenylalanine. Prior adrenodemedullation abolished the hyperglycemia elicited by p-chloroamphetamine. p-Chloroamphetamine-induced hyperglycemia was prevented by methysergide, which blocks the 5-HT1 and 5-HT2 receptor, the 5-HT1A/1B/2C receptor antagonist, (-)-propranolol, the selective 5-HT1A receptor antagonist, 4-(2'-methoxyphenyl-1-[2'-n-2"pyridinyl)-p-iodobenzamido]-ethyl-pi perazine (p-MPPI), the 5-HT2A/2B/2C receptor antagonists, ritanserin and 4-isopropyl-7-methyl-9-(2-hydroxy-1-methyl-propoxycarbonyl)-4,6A,7 ,8,9,10,10A-octahydro-indolo[4,3-FG]quinolone maleate(LY 53857). However, the 5-HT3 and 5-HT4 receptor antagonist, tropisetron, the 5-HT4 receptor antagonist, 2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester (SDZ 205-557), and the 5-HT2A receptor antagonist, ketanserin, did not affect the p-chloroamphetamine-induced hyperglycemia. These results suggest that p-chloroamphetamine-induced hyperglycemia is elicited by an enhanced 5-HT release and facilitated adrenaline release. Moreover, our results indicate that p-chloroamphetamine-induced hyperglycemia is mediated by 5-HT1A and 5-HT2B/2C receptors.
Yamada
J
J
Department of Pharmacology, Kobe Pharmaceutical University, Japan.
Sugimoto
Y
Y
Yoshikawa
T
T
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D000313:Adrenal Medulla / Q000502:physiology; D000315:Adrenalectomy; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004873:Ergolines / Q000494:pharmacology; D010134:Fenclonine / Q000494:pharmacology; D006943:Hyperglycemia / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D007211:Indoles / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D000077526:Tropisetron; D010133:p-Chloroamphetamine / Q000494:pharmacology*; D062366:para-Aminobenzoates
D000631:Aminopyridines; D001786:Blood Glucose; D004873:Ergolines; D007211:Indoles; D010879:Piperazines; D044403:Receptor, Serotonin, 5-HT2B; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D062366:para-Aminobenzoates; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; D016713:Ritanserin; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D012701:Serotonin; D010133:p-Chloroamphetamine; D000077526:Tropisetron; D007650:Ketanserin; D011433:Propranolol; C032663:LY 53857; D010134:Fenclonine; D010129:4-Aminobenzoic Acid; D008784:Methysergide