Contribution of monoaminergic nervous system in potentiation of 2-sec-butylphenyl N-methylcarbamate (BPMC) toxicity by malathion in male mice.
Malathion-induced marked potentiation of BPMC toxicity (about fivefold) was analyzed by measuring LD50 as an index of acute toxicity. The acute lethality of BPMC was decreased by muscarinic blockers (atropine, methylatropine, or trihexyphenidyl) or a monoamine oxidase inhibior (pargyline) and increased by a monoamine depleter (reserpine) or a dopaminergic blocker (haloperidol). The potentiation observed with BPMC and malathion was decreased by the muscarinic blockers, monoamine depleters (reserpine, alpha-methyl-p-tyrosine), an alpha-noradrenergic blocker (phentolamine), or haloperidol. The acute toxicities of other N-methylcarbamates MPMC (3,4-dimethylphenyl N-methylcarbamate), MTMC (3-methylphenyl N-methylcarbamate), NAC (1-naphthyl N-methylcarbamate), and XMC (3,5-dimethylphenyl N-methylcarbamate) were potentiated by malathion to a lesser degree than that of BPMC. Atropine protected against the lethalities of all N-methylcarbamates. Reserpine or haloperidol potentiated the lethalities of N-methylcarbamates with a similar tendency toward malathion. When the inhibitory effect of each N-methylcarbamate on brain acetylcholinesterase (AChE) was compared with its LD50, among five N-methylcarbamates BPMC had particularly strong anti-AChE activity. This characteristic of BPMC was not observed after the treatment with reserpine. These results suggest that BPMC may act not only on cholinergic nerves as an anti-AChE, but also on monoaminergic nerves which antagonize the lethal cholinergic effect. Malathion might inhibit the effect of BPMC on the monoaminergic nerves, thereby markedly potentiating the lethal effect of BPMC.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002219:Carbamates / Q000633:toxicity*; D004357:Drug Synergism; D006220:Haloperidol / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity; D008294:Malathion / Q000633:toxicity*; D008297:Male; D051379:Mice; D009420:Nervous System / Q000187:drug effects*; D012110:Reserpine / Q000494:pharmacology
D002219:Carbamates; D007306:Insecticides; C019276:BPMC; D001285:Atropine; D012110:Reserpine; C036868:methyl carbamate; D000110:Acetylcholinesterase; D006220:Haloperidol; D008294:Malathion