オキサムニキン 化学特性,用途語,生産方法
効能
抗住血吸虫薬
説明
Oxamniquine was originally investigated in the 1960s and was found to have limited antiprotozoal
activity, with activity against Schi stosoma mansoni but no activity against the other two
schistosomal organisms. In addition, the drug is stage specific, with activity against cercariae and
very young schistosomula and adult worms. For reasons that remain unknown, the drug is more
effective against adult male worms than against female worms. The drug has structural similarity to
hycanthone, which is no longer used because of severe toxicity and teratogenic effects.
使用
Antischistosomal.
定義
ChEBI: A member of the class of quinolines that is 1,2,3,4-tetrahydroquinoline which is substituted at positions 2, 6, and 7 by (isopropylamino)methyl, hydroxymethyl, and nitro groups, respectively.
適応症
Oxamniquine (Vansil) is a tetrahydroquinoline that
stimulates parasite muscular activity at low concentrations
but causes paralysis at higher concentrations. The
drug may act by esterification and binding of DNA,
leading to the death of the schistosome by interruption
of its nucleic acid and protein synthesis. The fluke may
esterify oxamniquine to produce a reactive metabolite
that alkylates parasite DNA. Resistance results from
absent or defective esterifying activity of the drug.
Oxamniquine has a restricted range of efficacy, being
active only against S. mansoni infections.
Oxamniquine is given orally and is readily absorbed
from the intestinal tract. Peak concentrations in plasma
are obtained in about 3 hours. The drug is excreted in
urine mostly as a 6-carboxyl derivative.
Side effects include CNS toxicity with unsteadiness
and occasionally seizures, especially in patients with a
history of seizures. It is contraindicated in pregnancy.
抗菌性
Activity is restricted to
Schistosoma mansoni. Some strains, particularly those in Egypt and Southern Africa, require higher doses for efficacy owing to innate tolerance.
応用例（製薬）
A synthetic quinolinemethanol, available for oral administration.
作用機序
Oxamniquine is activated via esterification to a biological ester that spontaneously dissociates to
an electrophile, which alkylates the helminth DNA, leading to irreversible inhibition of nucleic acid
metabolism. Resistant helminths do not esterify oxamniquine; therefore, activation
does not occur. Other metabolic reactions consist of oxidative reactions, leading to inactivation. The metabolites are excreted primarily in the urine.
薬物動態学
It is rapidly absorbed after oral administration, achieving a
peak concentration of 0.3–2.5 mg/L 1–3 h after an oral dose
of 15 mg/kg body weight. Peak levels following intramuscular
treatment at 7.5 mg/kg generally do not exceed 0.15 mg/L. It
is extensively metabolized to biologically inactive 6-carboxylic
and 2-carboxylic acid derivatives, which are excreted in the
urine, mostly within 12 h.
臨床応用
Infection with S. mansoni
副作用
Dizziness, sleepiness, nausea and headache occur frequently.
Other side effects are probably due to the death and disintegration
of the worms in the liver. Following treatment, urine
may become red.
安全性プロファイル
Poison by ingestion, intraperitoneal and intramuscular routes. Human mutation data reported. An antischistosomal agent. When heated to decomposition it emits toxic fumes of NOx.
オキサムニキン 上流と下流の製品情報
原材料
準備製品