1,2,3,4,10,14b-ヘキサヒドロ-2-メチルピラジノ[2,1-a]ピリド[2,3-c][2]ベンゾアゼピン 化学特性,用途語,生産方法
説明
Mirtazapine is an antidepressant launched in the Netherlands.
Mirtazapine is a potent antagonist of presynaptic α2 receptors as well as a
moderately potent 5-HT antagonist. Studies suggested that blockade of α2-adrenoceptors,
but not inhibition of noradrenaline uptake, is involved in the
mechanism of the antidepressant action of mirtazapine. Mirtazapine has
demonstrated efficacy in various studies in depressed patients, being equal or more
potent than mianserin, amitriptyline, etc. and exhibiting less anticholinergic and
gastrointestinal side effects and low cardiovascular toxicity. In addition to its
antidepressant effects, studies in animals indicated that mirtazapine has anxiolytic
andor hypnotic activity.
化学的特性
White Crystalline Solid
使用
An a 2-Adrenergic blocker. An analogue of Mianserin. Antidepressant
生物学の機能
Mirtazapine (Remeron) enhances both serotonergic
and noradrenergic neurotransmission. By blocking
presynaptic α
2-adrenoceptors, mirtazapine causes release
of norepinephrine. Indirectly, through noradrenergic
modulation of serotonin systems, mirtazapine also
causes increased release of serotonin. It is an antagonist at the 5-HT
2A, 5HT
2C, 5-HT
3, and histamine receptors
but has minimal affinity for muscarinic or α
1-receptors.
Mirtazapine does not inhibit neuronal reuptake of serotonin
or norepinephrine.Weight gain and sedation are
common side effects; sedation necessitates
dosing at bedtime. Mirtazapine does not have significant
effects on cytochrome P450 isoenzymes.
一般的な説明
Mirtazapine (Remeron) is another example of tetracyclicα2-blockers that shows selectivity for α2-receptorsversus 1-receptors. Blockade of central α2-receptors resultsin an increased release of NE and serotonin. This hasprompted its use as an antidepressant. This agent also hasactivity at nonadrenergic receptors. It is a potent blockerof 5-HT2 and 5-HT3 serotonin receptors and at histamineH1-receptors.
作用機序
Animal studies indicate that the efficacy of mirtazapine as an antidepressant results from enhancing central
noradrenergic and serotonergic activity, possibly through blocking central presynaptic α2-adrenergic
receptors. Blocking these receptors inhibits the negative feedback loop, which increases the release of NE
into the synapse. Mirtazapine also is a potent antagonist at 5-HT2 and 5-HT3 receptors, and it shows no
significant affinity for 5-HT1A or 5-HT1B receptors. Additionally, it displays some anticholinergic properties,
and it produces sedative effects (because of potent histamine H1 receptor antagonism) and orthostatic
hypotension (because of moderate antagonism at peripheral α1-adrenergic receptors). Its antidepressant
effect is comparable to the TCAs and may be better than some SSRIs, especially in patients with depression
of the melancholic type, but at higher doses, it may cause drowsiness and weight gain. The drug generally is
well tolerated, producing no more adverse events (including anticholinergic events) than the SSRIs and fewer
adverse events than the TCAs.
Mirtazapine absorption is rapid and
complete, with a bioavailability of approximately 50% as a result of first-pass metabolism. The rate and extent
of mirtazapine absorption are minimally affected by food. Dose and plasma levels are linearly related over a
dose range of 15 to 80 mg. The elimination half-life of the (–)-enantiomer is approximately twice that of the
(+)-enantiomer. In females of all ages, the elimination half-life is significantly longer than in males (mean
half-life, 37 versus 26 hours).
臨床応用
Mirtazapine is a piperazinodibenzoazepine antidepressant that is an isostere of the antidepressant mianserin. A seemingly simple isosteric replacement of an aromatic methine group (CH) in mianserin with a
nitrogen to give a pyridine ring (mirtazapine) has profound effects on the physicochemical properties,
pharmacokinetics, mechanisms of action, and antidepressant activities. Profound
differences between receptor affinity and transporter affinity, pharmacokinetics, regioselectivity in the formation of metabolites, and toxicity are observed for mianserin and mirtazapine and their antidepressant
mechanisms of action. The pyridine ring increases the polarity of the molecule and decreases the measured
partition coefficient and the basicity. Mianserin is a potent inhibitor of NET , whereas mirtazapine has
negligible effects on the inhibition of NET (pKi = 7.1 vs. 5.8 respectively).
1,2,3,4,10,14b-ヘキサヒドロ-2-メチルピラジノ[2,1-a]ピリド[2,3-c][2]ベンゾアゼピン 上流と下流の製品情報
原材料
準備製品