Effects of NIK-247 and tacrine on muscarinic receptor subtypes in rats.
1. The purpose of this study was to compare the effect of NIK-247 on muscarinic receptor subtypes with that of tacrine (THA) in rats. 2. NIK-247 and tacrine dose dependently inhibited the binding of [3H]pirenzepine (M1), [3H]AF-DX 384 (M2), and [3H]4-DAMP (M3). The IC50 values for NIK-247 were 4.4 x 10(-6) M, 1.1 x 10(-5) M, and 1.5 x 10(-5) M, respectively, whereas those for tacrine were 5.8 x 10(-7) M, 2.0 x 10(-6) M, and 5.8 x 10(-6) M, respectively. 3. Gpp[NH]p, a GTP analogue, slightly shifted the curve of displacement of [3H]AF-DX. 384 binding for NIK-247 to the right. However, Gpp[NH]p did not shift the curve of displacement of [3H]pirenzepine and [3H]4-DAMP binding to the right. 4. NIK-247 moderately decreased the rate of beating in right atrial preparations, but did not decrease it below 50% of control level. 5. These findings indicate that NIK-247 is an M1 antagonist, M2 partial agonist, and M3 antagonist.
Kojima
J
J
Omiya Research Laboratory, Nikken Chemicals Co., Ltd., Saitama, Japan.
Onodera
K
K
D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002217:Carbachol / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D018721:Muscarinic Agonists / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000378:metabolism; D013619:Tacrine / Q000494:pharmacology*
D000634:Aminoquinolines; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D011619:Psychotropic Drugs; D011976:Receptors, Muscarinic; D013619:Tacrine; D002217:Carbachol; C049860:amiridine