The new muscarinic M1-receptor agonist YM796 evokes yawning and increases oxytocin secretion from the posterior pituitary gland in rats.
The present experiments were performed to examine the effects of a new muscarinic M1-receptor agonist, (-)-YM796 ((-)-S-2,8-dimethyl-3-methylene-1-oxa-8-azaspiro[4.5]decane L-tartrate monohydrate), on yawning and oxytocin secretion from the posterior pituitary gland in rats YM796, at doses of 2.5-50 mg/kg (SC), elicited yawning. The yawning response was markedly increased by pretreatment with a beta-adrenoceptor antagonist, pindolol (20 mg/kg, IP), which per se did not elicit yawning. The yawning induced by YM796 (10 mg/kg, SC) in combination with pindolol (20 mg/kg, IP) was inhibited by scopolamine (0.5 mg/kg, SC), a muscarinic receptor antagonist, and pirenzcpine (300 micrograms/ rat, ICV) and EEDQ (N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline) (5 mg/kg, IP), muscarinic M1-receptor antagonists, but not by spiperone (0.5 mg/kg, SC), a dopamine D2-receptor antagonist, 4-DAMP (4-diphenylacetoxy-N-methylpiperidine methiodide) (100 micrograms/rat, ICV), a muscarinic M3-receptor antagonist, and [d(CH2)5, Tyr(Mc)2, Orn8]-vasotocin (100 ng/rat, ICV), an oxytocin receptor antagonist. YM796 at 2.5-50 mg/kg (SC) did not exert an action on prolactin levels but increased oxytocin secretion from the posterior pituitary gland in rats. This augmentation of oxytocin secretion by YM796 was inhibited by scopolamine (0.5 mg/kg, SC) and pirenzepine (3 mg/kg, SC), but not by mecamylamine (1 mg/kg, IP), a nicotinic receptor antagonist. The present findings obtained with YM796 suggest that the muscarinic M2-receptor stimulation participates in causing yawning behavior and oxytocin secretion in rats.
Fujikawa
M
M
Department of Pharmacology, Fukuoka University, Japan.
Yamada
K
K
Nagashima
M
M
Domae
M
M
Furukawa
T
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D018492:Dopamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007276:Injections, Intraventricular; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010121:Oxytocin / Q000378:metabolism*; D010277:Parasympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D013141:Spiro Compounds / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015000:Yawning / Q000187:drug effects*
C067766:2,8-dimethyl-3-methylene-1-oxa-8-azaspiro(4,5)decane; D000319:Adrenergic beta-Antagonists; D018492:Dopamine Antagonists; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D018045:Receptors, Oxytocin; D013141:Spiro Compounds; D010121:Oxytocin; D010869:Pindolol