アトモキセチン塩酸塩 化学特性,用途語,生産方法
外観
白色～ほとんど白色粉末～結晶
効能
中枢神経刺激薬, 選択的ノルアドレナリン再取り込み阻害薬
商品名
アトモキセチン (共和薬品工業); ストラテラ (日本イーライリリー); ストラテラ (日本イーライリリー)
説明
Atomoxetine is the first non-stimulant marketed for the treatment of attention deficit
hyperactivity disorder (ADHD). It is the R-stereoisomer of the racemate tomoxetine and
is a selective and potent norepinephrine uptake inhibitor (K
i=0.7–1.9 nM) that is
devoid of binding to monoamine receptor. It also has little effect on dopamine and
serotonin reuptake or acetylcholine, H1 histamine, alpha1 or alpha1-adrenergic or
dopamine receptors. It is prepared from racemic 1-phenylbut-3-en-1-ol via a selective
enzymatic acylation leaving the desired S-stereoisomer as the alcohol. This alcohol is
converted via a Mitsunobu reaction with ortho-cresol to the corresponding ether with
isomeric R-configuration. Ozonolysis and reduction steps provided the terminal alcohol
that is mesylated and displaced with methylamine. Its selectivity for norepinephrine
relative to dopamine inhibition was demonstrated in vivo preclinically. In a two-lever
(two condition) discriminative stimulus effect study in squirrel monkeys, tomoxetine
and other norepinephrine uptake inhibitors substituted for cocaine under low-dose
training conditions, whereas dopamine uptake inhibitors substituted for cocaine in both
low and high-dose conditions. In clinical ADHD studies in adolescents, it was
significantly different from placebo in 1.2 and 1.8 mpk/day dosing. In the clinical study
in adults using the CAARS scale a 95 mg/day dose provided greater than 30%
improvement in total scores. Atomoxetine is about 63% orally bioavailable, is highly
protein bound (98%, primarily to albumin) and has a half-life of about 5.2 h. It is
metabolized by CYP2D6 resulting in differential clearance for poor metabolizers (halflife
of 19 h with a 10 times higher AUC) relative to extensive metabolizers. The total
daily dose for children, adolescents and adults is a maximum of 100 mg/day. Common
side effects in children and adults include nausea, decreased appetite, and dizziness.
Adults may also have insomnia.
化学的特性
White Solid
使用
Atomoxetine hydrochloride, a Norepinephrine reuptake inhibitor, is used as a Psychotherapeutic and anti-depressant. These Secondary Standards are qualified as Certified Reference Materials. These are suitable for use in several analytical applications, including but not limited to pharma release testing, pharma method development for qualitative and quantitative analyses, food and beverage quality control testing, and other calibration requirements. Atomoxetine hydrochloride may be used as a pharmaceutical reference standard for determining atomoxetine hydrochloride in pharmaceutical formulations by spectrophotometric method.
定義
ChEBI: The hydrochloride salt of atomoxetine.
一般的な説明
Atomoxetine hydrochloride is a nonstimulant used in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children and adults.
生物活性
Potent and selective noradrenalin re-uptake inhibitor (K i values are 5, 77 and 1451 nM for inhibition of radioligand binding to human NET, SERT and DAT respectively). Displays minimal affinity for a range of other neurotransmitter receptors and transporters (K i > 1 μ M). Antidepressant.
アトモキセチン塩酸塩 上流と下流の製品情報
原材料
準備製品