Mianserin effects

The catecholamine-releasing agent beta-phenylethylamine (PEA) also produces the 5-HT syndrome (156) by direct activation of 5-HT receptors. The 5-HT antagonists methysergide and mianserin blocked the syndrome-producing effects of PEA, while depletion of 5-HT by PCPA or 5,7-DHT treatments was not effective. A possible role of catecholamines in the syndrome-producing effects of PEA cannot presently be discounted. 

Antidepressant Some animal models show antidepressant effects of lobelia extract (Subarnas et al. 1992). Similar to imipramine and mianserin, beta-amyrin palmitate shows antidepressant-like effects in the forced-swimming test (Subarnas et al. 1993a). Whereas mianserin and beta-amyrin palmitate reduce locomotor activity induced by methamphetamine, imipramine increases it. It potentiates sodium pentobarbital-induced sleep more potently than imipramine, but less than mianserin. Collectively, the effects of beta-amyrin palmitate in behavioral and physiological assays suggests it may work in a manner more similar to mianserin than imipramine. However, the mechanism of antidepressant-like effects of lobelia is uncertain. It may be through the beta-amyrin palmitate s ability to release norepinephrine (Subarnas et al. 1993b). An antidepressant effect of lobelia has not been established in humans. 

Atypical Antidepressants. None of the so-called atypical antidepressants have been tested in the treatment of AN. However, mianserin, an antidepressant available in Europe, has been found to increase body weight in patients with various depressive disorders. Although bupropion (Wellbutrin, Zyban) has not been tested in the treatment of AN, it is effective in the treatment of BN. However, immediate-release bupropion is associated with an especially high risk for seizures in these patients and is therefore contraindicated in those with eating disorders. The seizure risk associated with sustained-release bupropion remains unclear at this time, as the doses studied have not been as high as those for immediate-release bupropion. 

Serendipity has played a major role in the discovery of most classes of psychotropic drugs. For example, the observation that the first antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, impeded the reuptake of biogenic amines into brain slices, or inhibited their metabolism, following their acute administration to rats, provided the experimenter with a mechanism that could be easily investigated in vitro. Such methods led to the development of numerous antidepressants that differed in their potency, and to some extent in their side effects (for example, the selective serotonin reuptake inhibitors) but did little to further the development of novel antidepressants showing greater therapeutic efficacy. The accidental discovery of atypical antidepressants such as mianserin led to the broadening of the basis of the animal models... 

We have attempted to characterize this response further and to define its pharmacology and its utility as a rapid vivo assay for octopaminergic agents, particularly for actions on the CNS (31). The response to OA is specific in that none of the other putative neuroeffectors tested induced a comparable effect with the exceptions of NE and dopamine, both of which are known to have octopaminergic actions of their own. The response to OA was blocked by typical octopaminergic antagonists such as phentolamine, metoclopramide and mianserin (Table II). 

Maprotiline and amoxapine are selective norepinephrine uptake inhibitors. They share most of the properties of the tricyclic antidepressants. Maprotiline has less sedating effect than mianserin and it is more epileptogenic than any other antidepressant. It shows considerable cardiotoxicity when taken in overdose. 

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. 

Some evidence indicates that other drugs with action on the serotonergic system may be associated with efficacy in OCD. Tryptophan, a precursor of serotonin, was shown in a small placebo-controlled study to have an effect size similar to that of the SSRls (S. A. Montgomery et al. 1992). Mianserin, which has 5-HTjq and 5-HT2C receptor affinities, has also been reported in a small placebo-controlled study to be more effective than placebo. This last result raises the possibility that 5-HTjp or 5-HT2C may be the more specific receptors for OCD. The provocation of obsessional symptoms by m-chloro-phenylpiperazine (mCPP), which also has affinities for 5-HT,p and 5-HT2C, reinforces this concept (Zohar et al. 1988a). 

We are not aware, however, of any studies, to date, that show that either mianserin or mirtazapine produces sustained adrenoceptor or h-HTj receptor blockade in humans. Indeed, in animals, mianserin has been reported not to block Oj adrenoceptors following long-term administration [Sugrue 1980]. Elsewhere it has been argued that the 5-HT2 antagonism might be important in the action of mianserin because the more selective Oj antagonists tested, to date, do not, by themselves, appear to be clearly effective antide-... 

Maeda Y, Hayashi T, Furuta H, et al Effects of mianserin on human sleep. Neuropsychobiology 24 198-204, 1990... 

Morgan K, Oswald I, Borrow S Effects of a single dose of mianserin on sleep. Br J Clin Pharmacol 10 525-527, 1980... 

Curran, H.V., Lader, M. The psychopharmacological effects of repeated doses of fluvoxamine, mianserin and placebo in healthy subjects. Eur. J. Clin. Pharmacol. 29, 601-607, 1986. 

Three double-blind studies found mianserin to be superior to placebo, but 15 studies found it to be slightly less effective than tertiary amine TCAs ( Table 7-4 and Table 7-6). 

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