Effect of YM796, a novel muscarinic agonist, on the impairment of passive avoidance response in senescence-accelerated mice.
We compared the effects of YM796 [(-)-S-2,8-dimethyl-3-methylene-1-oxa-8- azaspiro[4,5]-decane L-tartrate monohydrate], a novel muscarinic agonist, on passive avoidance response with those of the cholinomimetics AF102B [(+/-)-cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine hydrochloride] and NIK247 [9-amino-2,3,5,6,7,8-hexahydro1H-cyclopenta(b)- quinoline monohydrate hydrochloride] in senescence-accelerated mice. SAMP8@YAN (SAM-P/8, senescence-accelerated-prone substrain) showed an age-dependent shortening in the latency of step-through when compared with SAMR1/YAN (SAM-R/1, senescence-accelerated-resistant substrain). The shortened latency of step-through in SAMP8@YAN was prolonged by administration of YM796 (0.3 and 1 mg/kg, PO), AF102B (3 and 10 mg/kg PO), and NIK247 (30 mg/kg, PO) in a bell-shaped manner. In contrast, amitriptyline (10, 30, and 50 mg/kg, PO), with cholinolytic properties, had no effect on this shortened latency of step-through. These results suggest that YM796, AF102B, and NIK247 ameliorated the disturbance of learning behavior, presumably due to facilitation of the central cholinergic system in SAMP8@YAN mice and that SAMP8@YAN may be an appropriate age-dependent model of amnesia for evaluating pharmacological actions of drugs.
Suzuki
M
M
Pharmacology Department, Yamanouchi Pharmaceutical Co. Ltd., Tokyo, Japan.
Yamaguchi
T
T
Ozawa
Y
Y
Iwai
A
A
Yamamoto
M
M
D000375:Aging / Q000235:genetics* / Q000523:psychology*; D000634:Aminoquinolines / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D018721:Muscarinic Agonists / Q000494:pharmacology*; D011619:Psychotropic Drugs / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology*; D013876:Thiophenes
C067766:2,8-dimethyl-3-methylene-1-oxa-8-azaspiro(4,5)decane; D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D011619:Psychotropic Drugs; D011812:Quinuclidines; D013141:Spiro Compounds; D013876:Thiophenes; D000639:Amitriptyline; C049860:amiridine; C059240:cevimeline