Postjunctional effects of mianserin and its metabolites on the rat isolated anococcygeus muscle.

Abstract

After rat isolated anococcygeus muscle had been treated with 6-hydroxydopamine to abolish noradrenergic transmission, the effects of mianserin and its metabolites alone on tone and on the contractile responses to methacholine and phenylephrine were studied. Mianserin (greater than or equal to 3 X 10(-5) M) and 8-hydroxymianserin (greater than or equal to 3 X 10(-6) M), but not desmethylmianserin and mianserin-N-oxide, induced contractions. The contractions to mianserin were not altered by phentolamine, atropine, cyproheptadine, ouabain and verapamil but were reduced in tissues treated with indomethacin. Thus the responses to mianserin may, in part, be mediated by the synthesis of prostaglandins. Mianserin (10(-5) M) and 8-hydroxymianserin (10(-7)-10(-5) M) potentiated, mianserin-N-oxide had no effect, and desmethylmianserin (10(-7)-10(-5) M) inhibited methacholine-induced contractions. The inhibition of responses to phenylephrine was concentration-related with desmethylmianserin (10(-7)-10(-5) M) and mianserin-N-oxide (10(-6)-10(-5) M) but not with mianserin or 8-hydroxymianserin (10(-7)-10(-5) M). The effects of mianserin and its metabolites on responses to methacholine and phenylephrine were similar in the absence and presence of indomethacin. These results suggest that mianserin and 8-hydroxymianserin increase the tissue's sensitivity to methacholine by an action at the level, or distal to, the muscarine receptor. In addition to blocking alpha 1-adrenoceptors, mianserin and 8-hydroxymianserin may have another postjunctional action at, or beyond, the alpha 1-adrenoceptor.