Its elimination half-life is 21 to 61 hours. Mianserin is metabolized in the liver by the CYP2D6 enzyme via N- oxidation and N- demethylation. The bioavailability of mianserin is 20 to 30%. However, the actual evidence in support of this label has been regarded as poor. By antagonizing the somatodendritic and presynaptic α 2-adrenergic receptors which function predominantly as inhibitory autoreceptors and heteroreceptors, mianserin disinhibits the release of norepinephrine, dopamine, serotonin, and acetylcholine in various areas of the brain and body.Īlong with mirtazapine, although to a lesser extent in comparison, mianserin has sometimes been described as a noradrenergic and specific serotonergic antidepressant (NaSSA). īlockade of the H 1 and possibly α 1-adrenergic receptors has sedative effects, and also antagonism of the 5-HT 2A and α 1-adrenergic receptors inhibits activation of intracellular phospholipase C (PLC), which seems to be a common target for several different classes of antidepressants. Mianserin has been found to be a low affinity but potentially significant partial agonist of the κ-opioid receptor (K i = 1.7 μM EC 50 = 0.53 μM), similarly to some tricyclic antidepressants (TCAs). Conversely, it has low affinity for the muscarinic acetylcholine receptors, and hence lacks anticholinergic properties. As an H 1 receptor inverse agonist with high affinity, mianserin has strong antihistamine effects (e.g., sedation). More specifically, it is an antagonist/ inverse agonist at most or all sites of the histamine H 1 receptor, serotonin 5-HT 1D, 5-HT 1F, 5-HT 2A, 5-HT 2B, 5-HT 2C, 5-HT 3, 5-HT 6, and 5-HT 7 receptors, and adrenergic α 1- and α 2-adrenergic receptors, and additionally a norepinephrine reuptake inhibitor. Mianserin appears to exert its effects via antagonism of histamine and serotonin receptors, and inhibition of norepinephrine reuptake. The smaller the value, the more strongly the drug binds to the site. Values are K i (nM), unless otherwise noted. See also: Pharmacology of antidepressants and Tetracyclic antidepressant § Pharmacology Mianserin Site Mianserin should not be taken with apraclonidine, brimonidine, sibutramine, or the combination drug of artemether with lumefantrine. Mianserin can make antihistamines and antimuscarinics have stronger effects.
There is a risk of dangerously low blood pressure if people take mianserin along with diazoxide, hydralazine, or nitroprusside. It may decrease the efficacy of antiepileptic medications.Ĭarbamazepine and phenobarbital will cause the body to metabolize mianserin faster and may reduce its effects. Mianserin may enhance the sedative effects of drugs such as alcohol, anxiolytics, hypnotics, or antipsychotics when co-administered. Overdose of mianserin is known to produce sedation, coma, hypotension or hypertension, tachycardia, and QT interval prolongation.
Withdrawal Ībrupt or rapid discontinuation of mianserin may provoke a withdrawal, the effects of which may include depression, anxiety, panic attacks, decreased appetite or anorexia, insomnia, diarrhea, nausea and vomiting, and flu-like symptoms, such as allergies or pruritus, among others. Uncommon (0.1% Ĭommon (1% Very common (incidence>10%) adverse effects include constipation, dry mouth, and drowsiness at the beginning of treatment. If based on clinical decision, normal precautions should be exercised and the dosages of mianserin and any concurrent therapy kept under review and adjusted as needed. People with severe liver disease should not take mianserin, and it should be used with caution for people with epilepsy or who are at risk for seizures, as it can lower the threshold for seizures. While there is no evidence that it can harm a fetus from animal models, there is no data showing it safe for pregnant women to take. It should not be given, except if based on clinical need and under strict medical supervision, to people younger than 18 years old, as it can increase the risk of suicide attempts and suicidal thinking, and it can increase aggressiveness. It can also be used at lower doses (around 10mg/day) to treat insomnia. Mianserin at higher doses (30-90mg/day) is used for the treatment of major depressive disorder.