European journal of pharmacology
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We investigated the involvement of the sympatho-adrenal axis in the hyperthermia induced by methamphetamine by using a biotelemetric system. The intraperitoneal injection of methamphetamine (1 mg/kg) induced hyperthermia preceded by an increase in oxygen consumption in freely moving rats. The hyperthermic effect of methamphetamine was completely blocked by chemical sympathectomy with 6-hydroxydopamine (50 mg/kg, i.p.). ⋯ In adrenalectomized rats, dexamethasone supplementation (0.5 mg/kg, s.c.) restored the methamphetamine-induced hyperthermia. Furthermore, dantrolene (1 or 2 mg/kg, i.v.), which blocks Ca2+ release from the sarcoplasmic reticulum in skeletal muscle, attenuated the hyperthermia. These results suggest that methamphetamine stimulates norepinephrine release from sympathetic nerve terminals, which then enhances thermogenesis in skeletal muscle under the permissive action of glucocorticoids.
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Comparative Study
Effects of moguisteine on the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve in guinea pigs.
The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. ⋯ The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.
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We investigated the effect of the new potent and selective histamine H3 receptor agonist, immepip, and the histamine H3 receptor antagonist, clobenpropit, on in vivo neuronal histamine release from the anterior hypothalamic area of urethane-anesthetized rats, using microdialysis. Intrahypothalamic perfusion with immepip at concentrations of 1 and 10 nM reduced histamine release to 75% and 35% of its basal level, respectively. Peripheral injection of immepip (5 mg/kg) caused a sustained decrease in histamine release of 50%. ⋯ In conclusion, intrahypothalamic perfusion of the histamine H3 receptor agonist, immepip and the histamine H3 receptor antagonist, clobenpropit, potently and oppositely modulated in vivo histamine release from the anterior hypothalamic area. The decreased histamine release after peripheral injection of immepip indicates that this novel agonist readily crosses the blood-brain barrier, making it a potential candidate for in vivo histamine H3 receptor studies. The differential increase in histamine release after peripheral injection of clobenpropit and thioperamide is discussed.