Sympathoexcitatory action of a novel muscarinic receptor agonist, AF102B, and its blockade by pirenzepine.
The pharmacological effects of a novel, selective muscarinic (M1) receptor agonist, AF102B (cis-2-methyl-spiro-(1,3-oxathiolane-5,3')-quinuclidine hydrochloride hemihydrate), on sympathetic nerve activity are described. Intravenous administration of AF102B (1 and 10 mg/kg) produced a dose-dependent increase in cardiac sympathetic nerve activity accompanied by tachycardia in spinal-intact rats. In addition, AF102B (10 mg/kg) caused a marked increase in cardiac sympathetic nerve activity and heart rate in pithed rats. Pirenzepine (50 micrograms/kg) inhibited these sympathoexcitatory effects of AF102B (10 mg/kg) in pithed rats. These findings suggest that AF102B possesses a sympathoexcitatory action which is mediated by M1-receptors.
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
M
M
Yoshioka
H
H
Togashi
M
M
Matsumoto
K
K
Morii
H
H
Saito
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010277:Parasympathomimetics / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology*; D011812:Quinuclidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013566:Sympathomimetics; D013876:Thiophenes
D010277:Parasympathomimetics; D011812:Quinuclidines; D013566:Sympathomimetics; D013876:Thiophenes; D010890:Pirenzepine; C059240:cevimeline