Effect of mianserin on noradrenergic transmission in the rat anococcygeus muscle.
1 The effects of mianserin on the accumulation of (-)-[(3)H]-noradrenaline and on contractile responses to field stimulation, exogenously applied (-)-noradrenaline, and to tyramine were studied in the rat anococcygeus muscle.2 Mianserin (10(-9) to 10(-5) M) and nortriptyline (10(-9) to 10(-5) M) inhibited the accumulation of (-)-[(3)H]-noradrenaline. In this aspect mianserin had a similar potency to nortriptyline, the most potent tricyclic antidepressant in inhibiting noradrenaline accumulation in this tissue.3 Mianserin 10(-9) or 10(-8) M alone had no effect on contractile responses to field stimulation and to (-)-noradrenaline but inhibited the responses to tyramine. The responses to field stimulation at low frequencies and to (-)-noradrenaline were potentiated by 10(-7) and 10(-6) M mianserin. It is suggested that the inhibitory effect mianserin has on neuronal accumulation is primarily responsible for these effects. Mianserin 10(-5) M inhibited responses to field stimulation and to (-)-noradrenaline.4 In the presence of nortriptyline (10(-6) M), the contractile responses to field stimulations were potentiated by mianserin (10(-8), 10(-7) and 10(-6) M), 10(-8) M being the most potent in this aspect. Mianserin 10(-8), 10(-7), 10(-6) and 10(-5) M had a similar inhibitory effect on responses to (-)-noradrenaline. In the absence of neuronal uptake, the potentiating effect of mianserin on responses to field stimulation may be due to antagonism at presynaptic alpha-adrenoceptors. In the presence of 10(-6) M nortriptyline, 10(-5) M mianserin abolished responses to field stimulation.5 Following incubation of the tissue in the presence of 6-hydroxydopamine (10(-3) M for 3 h), mianserin (10(-7), 10(-6) and 10(-5) M) nortriptyline (10(-7) and 10(-6) M) and phentolamine (5 x 10(-8) and 5 x 10(-7) M) inhibited contractile responses to (-)-noradrenaline. This illustrates the ability of these agents to inhibit the responses to noradrenaline at a postsynaptic site. The inhibitory effect was dose-related with nortriptyline and phentolamine; this illustrates the ability of these agents to antagonize postsynaptic alpha-adrenoceptors. The inhibitory effect observed with mianserin was not dose-related. This suggests that in addition to its reported ability to antagonize postsynaptic alpha-adrenoceptors, mianserin may have another post-synaptic action at the level of, or distal to, the alpha-adrenoceptor.6 These results illustrate that, in the rat anococcygeus muscle, mianserin is a potent inhibitor of noradrenaline accumulation and may be an antagonist at presynaptic alpha-adrenoceptors. Mianserin also inhibits the responses to exogenously applied noradrenaline in this tissue by an action or actions at the level of, or distal to, the postsynaptic alpha-adrenoceptor.
D000818:Animals; D003984:Dibenzazepines / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008803:Mianserin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009132:Muscles / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000502:physiology*; D009661:Nortriptyline / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D013564:Sympathetic Nervous System / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D003984:Dibenzazepines; D006892:Hydroxydopamines; D008803:Mianserin; D009661:Nortriptyline; D009638:Norepinephrine; D010646:Phentolamine