Enhancement of systemic and CNS delivery of meptazinol hydrochloride by intranasal administration to rats / 药学学报

<p><b>AIM</b>To investigate the extent of systemic absorption and uptake of meptazinol (MEP) hydrochloride in cerebrospinal fluid (CSF) after intranasal administration on rats and compare with oral administration.</p><p><b>METHODS</b>CSF samples were collected by a serial sampling method. The concentration of MEP in the biological samples was measured by HPLC with fluorescence detector.</p><p><b>RESULTS</b>Rapid and significant levels of MEP in plasma and CSF can be achieved after nasal administration whereas the oral administration resulted in considerably lower drug concentrations. AUC in plasma and CSF from the nasal route are 7.375 and 15.6 folds compared with those of the oral route, respectively.</p><p><b>CONCLUSION</b>Intranasal MEP is able to show quick absorption and improve the bioavailability, which could be a promising alternative to oral administration.</p>

Antinociceptive effects of meptazinol and its isomers on carrageenan-induced thermal hyperalgesia in rats / 生理学报

Using the latency of paw withdrawal (PWL) from a noxious thermal stimulus as a measure of hyperalgesia, the effects of i.p. injection of meptazinol and its isomers, 112824 and 112825, on carrageenan-induced thermal hyperalgesia were studied in awaked carrageenan-inflamed rats. Peripheral inflammation was induced by intraplantar (i.pl.) injection of carrageenan (2 mg/100 microl) into one hindpaw in rats. Carrageenan produced marked inflammation (edema and erythema) and thermal hyperalgesia in the injected paws, which peaked at 3 h after injection and showed little change in magnitude for another 3 h. Injection of 0.1 mg/kg meptazinol (i.p.) at 3 h after carrageenan had no effect on the PWLs of either inflamed or non-inflamed hindpaw during the next 100 min (P>0.05, n=8). At the dosage of 1 and 10 mg/kg, meptazinol produced marked anti-nociception and anti-hyperalgesia in non-inflamed and inflamed hindpaw, respectively (P<0.05, n=8-11). The prolonging effect of meptazinol on PWL in inflamed hindpaw was more potent than that in non-inflamed hindpaw. Pre-administration of 1.5 mg/kg naloxone significantly antagonized meptazinol-induced anti-nociception and anti-hyperalgesia. Intraperitoneal injection of an isomer of meptazinol, 112825 (1.5 mg/kg), but not 112824 (1 mg/kg), markedly increased the PWL of the non-inflamed hindpaw. Nevertheless, both the isomers produced similar anti-hyperalgesic effect to that of meptazinol (P<0.05, n=8), which was completely reversed by naloxone (1.5 mg/mg). The results suggest that meptazinol and its isomers have anti-nociceptive and anti-hyperalgesic properties with the former more potent. The effects are mainly mediated by mu opioid receptors. This study provides an important clue for extending clinical utilization of meptazinol and its isomers.

Avaliaçäo clínica de um novo analgésico antagomista dos ópio: meptazinol / Clinical avaliation of a new analgesic opium antagonist: meptazinol

O efeito analgésico e, em especial, a segurança da administraçäo intramuscular de100 mg de meptazionol foram avaliados em estudo aberto, em 42 pacientes portadores de dor intensa ou muito intensa, resultante de causas diversas, tanto clinicas como pós-cirúrgicas. Os resultados indicaram que meptazinol é um analgésico eficaz, com poucos e toleráveis efeitos secundários, sendo a vertigem/tontura o mais freqüente, com incidência de 23,8%. O alívio da dor instalou-se em período inferior a 30 minutos, sendo máximo até 2 horas após a medicaçäo e perdurando pelo tempo de observaçäo clíncia, que foi de 6 horas, em grau entre acentuado e completo. Em relaçäo a sinais vitais e sedaçäo, näo existiu diferença clínica entre o período pré-administraçäo e os períodos de observaçäo, salientando-se portanto, a segurança do emprego do meptazimol