Effect of M4-cholinoceptor blockade on haloperidol-produced catatonic syndrome in rats.
We studied the relationship between the efficiency of muscarinic receptor antagonists in preventing haloperidol-induced catatonia and their activity in tests for the interaction of ligands with various subtypes of muscarinic receptors (M1-M4) in rats. Mathematical modeling showed that affinity of the ligand for M4 receptors positively affects its ability to correct extrapyramidal disorders (catatonic syndrome) produced by haloperidol, while affinity for M2 receptors had a negative effect on this characteristic.
Dagaev
S G
SG
Institute of Toxicology, Russian Ministry of Health, St. Petersburg, Russia.
Kosmachev
A B
AB
Filko
O A
OA
Kubarskaya
L G
LG
Khrabrova
A V
AV
Beliaev
V A
VA
Podosinovikova
N P
NP
Libman
N M
NM
Sanotskii
V I
VI
Dolgo-Saburov
V B
VB
D000818:Animals; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D002389:Catatonia / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D006220:Haloperidol / Q000633:toxicity*; D007700:Kinetics; D008024:Ligands; D008297:Male; D008954:Models, Biological; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D043588:Receptor, Muscarinic M4 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000145:classification / Q000378:metabolism; D013577:Syndrome
D008024:Ligands; D018727:Muscarinic Antagonists; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D006220:Haloperidol