Selective blockade in vivo of cardiac muscarinic M2 receptors by a polymethylene tetramine, BHC-9C.
The antimuscarinic effects of BHC-9C (N,N'-bis[6-[(2-methoxybenzyl)amino]hexyl]-1,9-nonanediamine tetrahydrochloride), a member of a series of polymethylene tetraamines with unprecedented in vitro selectivity for cardiac muscarinic M2 receptors, were assessed in several in vivo test systems. BHC-9C (300 micrograms/kg i.v.) proved to be a potent antagonist at cardiac M2 receptors that mediate the decrease in heart rate in the pithed rat. In contrast, it displayed no considerable blocking activity at vascular M2 receptors subserving vasodepression and at ganglionic M1 receptors that mediate cardiovascular stimulation in the anaesthetized and pithed rat, respectively. These in vivo data are consistent with the suggestion based on in vitro experiments that BHC-9C is a highly selective antagonist of cardiac muscarinic M2 receptors.
Wess
J
J
Faculty of Biochemistry, Pharmacy and Food Chemistry, Department of Pharmacology, University of Frankfurt/M, F.R.G.
Lambrecht
G
G
Mutschler
E
E
Melchiorre
C
C
Angeli
P
P
D000758:Anesthesia; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D003655:Decerebrate State; D003959:Diamines / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*
D003959:Diamines; D010276:Parasympatholytics; D011976:Receptors, Muscarinic; C054696:BHC-9C; D010890:Pirenzepine; D001285:Atropine