tetano
Editor, Senior Moderator
Basic Clin Pharmacol Toxicol. 2013 Feb 8. doi: 10.1111/bcpt.12058. [Epub ahead of print]
Reduction of Sympathetic Nerve Activity as a Possible Mechanism for the Hypothermic Effect of Oseltamivir, an Anti-influenza Virus Drug, in Normal Mice.
Ono H, Iwajima Y, Nagano Y, Chazono K, Maeda Y, Ohsawa M, Yamamoto S.
Source
Laboratory of CNS Pharmacology, Nagoya City University, Mizuho-ku, Nagoya, Japan.
Abstract
Oseltamivir, an anti-influenza virus drug, has strong antipyretic effects in mice (Ono et al., 2008) and influenza patients. 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.-preadministered 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.
? 2013 The Authors Basic & Clinical Pharmacology & Toxicology ? 2013 Nordic Pharmacological Society.
PMID:
23398656
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23398656
Reduction of Sympathetic Nerve Activity as a Possible Mechanism for the Hypothermic Effect of Oseltamivir, an Anti-influenza Virus Drug, in Normal Mice.
Ono H, Iwajima Y, Nagano Y, Chazono K, Maeda Y, Ohsawa M, Yamamoto S.
Source
Laboratory of CNS Pharmacology, Nagoya City University, Mizuho-ku, Nagoya, Japan.
Abstract
Oseltamivir, an anti-influenza virus drug, has strong antipyretic effects in mice (Ono et al., 2008) and influenza patients. 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.-preadministered 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.
? 2013 The Authors Basic & Clinical Pharmacology & Toxicology ? 2013 Nordic Pharmacological Society.
PMID:
23398656
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/23398656