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. 1980 Feb;68(2):241–250. doi: 10.1111/j.1476-5381.1980.tb10413.x

Effect of mianserin on noradrenergic transmission in the rat anococcygeus muscle

Sheila A Doggrell
PMCID: PMC2043912  PMID: 6244037

Abstract

1 The effects of mianserin on the accumulation of (-)-[3H]-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 (-)-[3H]-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 α-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 × 10-8 and 5 × 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 α-adrenoceptors. The inhibitory effect observed with mianserin was not dose-related. This suggests that in addition to its reported ability to antagonize postsynaptic α-adrenoceptors, mianserin may have another post-synaptic action at the level of, or distal to, the α-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 α-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 α-adrenoceptor.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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