ゾルミトリプタン 化学特性,用途語,生産方法
外観
白色～黄赤色～緑色粉末～結晶
効能
抗片頭痛薬, 血管収縮薬, セロトニン受容体作動薬
商品名
ゾーミッグ (沢井製薬); ゾーミッグ (沢井製薬)
説明
Zolmitriptan is a selective serotonin receptor agonist of the 1B and 1D subtypes. It is mainly used in the acute treatment of migraine attacks with or without aura and cluster headaches. Zolmitriptan takes effect through binding to human 5-HT1Band 5-HT1Dreceptors, leading to cranial blood vessel constriction and the release of sensory neuropeptides through nerve endings in the trigeminal system.
化学的特性
White Crystalline Powder
使用
Zolmitriptan is a serotonin 5HTID-receptor agonist and used to treat migraine (1,2,3).
一般的な説明
Zolmitriptan, the second triptan marketed (approved in1997), has a much better bioavailability (40%–48%) thansumatriptan. It is rapidly absorbed after oral or nasal sprayadministration. It also has an orally disintegrating tablet formulation(Zomig ZMT), which can be taken without water.Zolmitriptan undergoes rapid N-demethylation via CYP1A2to a more potent, active metabolite, N-desmethylzolmitriptan,which is 2 to 6 times more potent than the parentdrug. This active metabolite was detected 5 minutesafter dosing and accounts for about two thirds of the plasmaconcentration of the administered dose of the parent drug.284Thus, it is reasonable to assume that the therapeutic effectsand especially the CNS side effects of zolmitriptan must bein part attributed to the plasma levels of this active metabolite,at least until it is further degraded by hepatic MAO-Ato its inactive indole acetic acid derivatives.
臨床応用
Zomig was launched in Germany, Denmark, Sweden and the UK for use as
an antimigraine agent (with and without aura). It can be prepared by three related
routes of 5 to 7 steps starting from L-4-nitrophenylalanine. Zomig is a 5-HT
1D/1B receptor agonist (10 fold ratio) with modest (< 100x) affinity for 5-HT
1A and 5-HT
1F receptors. It has no affinity for other serotonin receptors or receptors of other
neurotransmitters. It has a novel dual action mechanism: centrally it acts on the
trigeminal nucleus caudalis and peripherally is acts on the trigeminovascular system.
Zomig was effective in treating headaches and nonheadache (photophobia,
phonophobia and nausea) symptoms. It was 2-3 times more potent than sumatriptan
and is metabolized to three compounds, one of which is 2-8 times more active than the
parent. It caused a 40-50% decrease in headache after 1 h and a 73-77% after 4 h.
There was a 30% reoccurance of headache but 90% effective treatment with a second
dose. It blocks neurogenic inflammation by inhibiting release of peptides, causes
vasoconstriction, and inhibits neuronal depolarization at peripheral sites in the
cranium. It is 40% bioavailable and a 10 time theraputic dose showed no safety
concerns.
参考文献
https://www.drugbank.ca/drugs/DB00315
Rothner, A. D., et al. "Zolmitriptan oral tablet in migraine treatment: high placebo responses in adolescents." Headache the Journal of Head & Face Pain 46.1(2006):101.
Hedlund, C, et al. "Zolmitriptan nasal spray in the acute treatment of cluster headache: a meta-analysis of two studies. " Neurology49.9(2009):1315–1323.
ゾルミトリプタン 上流と下流の製品情報
原材料
準備製品