2809 Mirtazapine Mirtazapine is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is the only tetracyclic antidepressant that has been approved by the Food and Drug Administration to treat depression. 61337-67-5 4205 C17H19N3 265.157900 White powder. 114-116°C Slight Oral. Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%. Mirtazapine acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT₁ receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazapine also acts as a weak antagonist at 5-HT₁ receptors and as a potent antagonist at 5-HT₂ (particularly subtypes 2A and 2C) and 5-HT₃ receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazapine also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazapine has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors. Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hydroxy metabolite of mirtazapine, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. Several metabolites possess pharmacological activity, but plasma levels are very low. Route of Elimination: This drug is known to be substantially excreted by the kidney (75%). Half Life: 20-40 hours LD50: 600-720mg/kg (oral, mice) (L1855) LD50: 320-490mg/kg (oral, rat) (L1855) No indication of carcinogenicity to humans (not listed by IARC). For the treatment of major depressive disorder. Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia. Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion or exchange transfusion in the treatment of mirtazapine overdosage. No specific antidotes for mirtazapine are known. (L1712) 2009-07-21T20:26:43Z 2014-12-24T20:25:51Z Mirtazapine C07570 6950 Mirtazapine DB00370 true CN1CCN2C(C1)C1=CC=CC=C1CC1=C2N=CC=C1 C17H19N3 InChI=1/C17H19N3/c1-19-9-10-20-16(12-19)15-7-3-2-5-13(15)11-14-6-4-8-18-17(14)20/h2-8,16H,9-12H2,1H3 InChIKey=RONZAEMNMFQXRA-UHFFFAOYNA-N 265.3529 265.157897623 Exogenous Solid 2.9 HMDB14514 CHEMBL654 4060 <p>Leonid Metzger, &#8220;Methods for the preparation of mirtazapine intermediates.&#8221; U.S. Patent US20020165238, issued November 07, 2002.</p>