Noradrenaline Mianserin

Known as a noradrenaline and specific serotonin antidepressant (NaSSA). More potent affinity for alpha-2 adrenoceptors and 5-HT receptors than mianserin HI antagonist... 

Mirtazepine (called a Noradrenaline and Selective Serotonin Antidepressant NaSSA) is the 6-aza derivative of mianserin and shares several important pharmacological properties with its predecessor, namely its antihistaminic and alpha-1 adrenoceptor antagonistic actions. Like mianserin, mirtazepine also causes weight gain. Nevertheless, mirtazepine is better tolerated and there is no evidence of blood dyscrasias associated with its clinical use. 

Figure 7.4. Summary of the site of action of mirtazepine (NaSSA). The inhibitory 2 adrenoceptors facilitate the release of both noradrenaline and serotonin (via the heteroceptor on the 5-HT neuron). This is further enhanced by the receptor on the serotonin cell body. Thus mirtazepine (and to a lesser extent mianserin) enhance both noradrenergic and serotonergic...

The triazolopyridine trazodone does not have an appreciable effect on the re-uptake of the neurotrans-mittors dopamine or noradrenaline. It is a weak inhibitor of serotonin re-uptake but is a potent antagonist of the serotonin 5-HT2 receptor. Clinical experience has shown unpredictable efficacy. Trazodone has little antimuscarinic activity and has little if any action on cardiac conduction. Like mianserin it can therefore safely be used in patients for which anticholinergics are contraindicated and there are no absolute contraindications for patients with concomitant diseases of the cardiovascular system. 

The antidepressant mirtazapine is pharmacologically similar to mianserin. It has a slightly weaker blocking action at i-adrenoceptors, and this is claimed to give it a dual mode of action, increasing the release of both noradrenaline and serotonin (1). It is claimed to have a more rapid onset of action than some SSRIs, but this may be due to its prominent sedative effect, which improves insomnia from the start of treatment. 

Depression ( -Antagonists Enhance noradrenaline release Mianserin... 

Evidence accumulated in 1978 for a catecholamine receptor supersensitivity theory of depression. 8 The therapeutic action of antidepressants may be due to delayed post-synaptic changes in receptor sensitivity, rather than to acute events like uptake. Various drugs, including TCA, mianserin, viloxazine and iprindol, as well as electroconvulsive therapy (ECT), but not selective 5-HT uptake inhibitors, caused central alpha-adrenoceptor subsensitivity in rats as measured by noradrenaline (NA)-associated adenylate cyclase or by receptor binding. In vivo, the effects were associated with chronic but not acute treatment, paralleling the clinical effects. MAOI may cause similar effects on chronic but not acute treatment. , 24-27 Brain NA turnover in rats was decreased by chronic desipramine and other TCA, but unaffected by iprindol and increased by mianserin.3,28... 

Mianserin and maprotiline are tetracyclic antidepressants, which have actions similar to those of the tricyclie antidepressants. However, while the tetracyclics are more sedating, their antimusearinic effects are less marked. Maprotiline inhibits the leuptake of noradrenaline (norepinephrine) and has weak affinity for eentral adrenergic (aj) receptors. Mianserin does not prevent the peripheral reuptake of noradrenaline it blocks presynaptic adrenergic (a2) receptors and increases the turnover of hrain noradrenaline. It is also an antagonist of serotonin receptors in some parts of the brain. 

The pressor (increased blood pressure) responses to tyramine and noradrenaline (norepinephrine) in depressed patients remained virtually unchanged after 14 days of treatment with mianserin 60 mg daily.In 5 healthy subjects taking maprotiline the pressor response to tyramine was reduced threefold while the noradrenaline response remained unchanged. ... 

Coppen A, Ghose K, Swade C, Wood K. Effect of mianserin hydrochloride on peripheml uptake mech sms for noradrenaline and 5-hydroxytryptamine in maa BrJ Clin Pharmacol (1978) 5, 13S-17S. 

Ghose K. Studies on the interaction between mianserin and noradrenaline in patients sufferii from depressive illness. BrJ Clin Pharmacol (1977) 4,712-14. 

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