[The role of the blockade of separate subtypes of muscarinic receptors in realizing the antidotal effect of m-cholinolytics in dimethyl dichlorovinyl phosphate poisoning].
On comparison of the values of receptor selectivity of a series of m-cholinoblockers in vitro with those of the selectivity of their effect in in vivo experiments, pharmacological tests characterizing the interaction of ligands with m1, m2, and m3-subtypes of muscarine receptors were determined. Analysis of the protective effect of m-cholinoblockers in poisoning with organophosphorus compounds (OPC) depending on their activity in the determined tests showed that blocking of the m1-cholinoceptors is responsible for the antidotal effect of the antagonists, whereas block ing of m2-cholinoceptors prevents it. It is suggested that the negative effect of m2-cholinoceptor blocking on the protective effect of the drugs in OPC poisoning is mediate d by increased excretion of the mediator into the synaptic cleft as a result of interaction of the ligands with the presynaptic autochol inoceptors.
Kosmachev
A B
AB
Institute of Toxicology, Ministry of Public Health, St. Petersburg, Russia.
Beliaev
V A
VA
Fil'ko
O A
OA
Podosinovikova
N P
NP
Solov'eva
N E
NE
Titkova
T A
TA
D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects; D004006:Dichlorvos / Q000506:poisoning*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006321:Heart / Q000187:drug effects; D007306:Insecticides / Q000506:poisoning*; D008024:Ligands; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use*; D011041:Poisoning / Q000188:drug therapy; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012469:Salivary Glands / Q000187:drug effects
D000931:Antidotes; D007306:Insecticides; D008024:Ligands; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D004006:Dichlorvos