Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oseltamivir phosphate (Tamiflu), an anti-influenza virus drug, is hydrolyzed by carboxylesterase to an active metabolite. The metabolite inhibits the influenza virus-specific neuraminidase. In this study, the effects of oseltamivir on normal core body temperature were studied in mice. Oseltamivir (30-300 mg/kg, intraperitoneally (i.p.) and 100-1000 mg/kg, orally (p.o.)) dose-dependently lowered the body temperature. The effects of oseltamivir (p.o.) continued longer than those of oseltamivir (i.p.), and approximately triple doses of oral oseltamivir were needed to produce the same peak effects as intraperitoneal oseltamivir. The non-steroidal anti-inflammatory drug diclofenac (1-30 mg/kg, i.p.) did not affect body temperature, and (at 30 and 60 mg/kg, s.c.) did not interact with the hypothermic effects of oseltamivir (100 mg/kg, i.p.). Zanamivir, which also inhibits neuraminidase, did not produce hypothermia at doses of 100 and 300 mg/kg, i.p. Clopidogrel (100, 300 mg/kg, i.p.), which is metabolized by the same carboxylesterase, tended to decrease the hypothermic effects of oseltamivir (100 mg/kg, i.p.). These results suggest that the hypothermic effects of oseltamivir are due to its hydrolytic metabolite, and that the hypothermia observed in mice has some relationship to the antipyretic effects and severe hypothermia (adverse event) observed in influenza patients after taking oseltamivir.
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PMID:Oseltamivir, an anti-influenza virus drug, produces hypothermia in mice. 1837 55

Oseltamivir, an anti-influenza virus drug, has strong antipyretic effects in mice (Biological and Pharmaceutical Bulletin, 31, 2008, 638) and patients with influenza. In addition, hypothermia has been reported as an adverse event. The prodrug oseltamivir is converted to oseltamivir carboxylate (OC), an active metabolite of influenza virus neuraminidase. In this study, core body temperature was measured in mice, and oseltamivir and OC were administered intracerebroventricularly (i.c.v.) or intraperitoneally (i.p). Low i.c.v. doses of oseltamivir and OC dose-dependently produced hypothermia. Zanamivir (i.c.v.), another neuraminidase inhibitor, did not produce hypothermia. These results suggested that the hypothermic effects of oseltamivir (i.p. and i.c.v.) and OC (i.c.v.) are not due to neuraminidase inhibition. OC (i.p.) did not lower body temperature. Although mecamylamine (i.c.v.) blocked the hypothermic effect of nicotine-administered i.c.v., the hypothermic effects of oseltamivir and OC (i.c.v.) were not blocked by mecamylamine (i.c.v.). The effect of oseltamivir (i.p.) was markedly increased by s.c.-pre-administered mecamylamine and also hexamethonium, a peripherally acting ganglionic blocker, suggesting their potentiating interaction at peripheral sites. The hypothermic effect of nicotine (i.c.v.) was decreased by lower doses of oseltamivir (i.c.v.), suggesting the anti-nicotinic action of oseltamivir. These results suggest that oseltamivir (i.p.) causes hypothermia through depression of sympathetic temperature regulatory mechanisms via inhibition of nicotinic receptor function and through unknown central mechanisms.
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PMID:Reduction in sympathetic nerve activity as a possible mechanism for the hypothermic effect of oseltamivir, an anti-influenza virus drug, in normal mice. 2339 56