Cholinergic agonists adverse effects

N-methylscopolamine (Costa et al. 1982b Schwab et al. 1983). Animals made tolerant to disulfoton were resistant to the lethal or adverse effects of cholinergic agonists, such as carbachol (Brodeur and DuBois 1964 Costa et al. 1981 Schwab and Murphy 1981) and oxotremorine (Costa et al. 1982b McPhillips 1969a), which are not hydrolyzed by acetylcholinesterase. Tissues from animals tolerant to disulfoton such as the ilea (Foley and McPhillips 1973 McPhillips 1969b McPhillips and Dar 1967) and the atria (Perrine and McPhillips 1970 Schwab et al. 1983), were resistant to the effects of carbachol and/or oxotremorine. Because the uterus and vas deferens have a relatively sparse parasympathetic innervation compared to the ileum and do not receive a steady flow of impulses via this system, these tissues were not as subsensitive to carbachol as the ileum (Foley and McPhillips 1973). Thus, acetylcholine accumulation may be a prerequisite for tolerance development. 

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