On the cholinergic component of action of meptazinol.

The effects of meptazinol, morphine and fentanyl on the indirect twitch contractions, the contractions produced by periarterial nerve stimulation, by field stimulation and by applied acetylcholine (ACh) were studied in rat isolated diaphragm and ileum respectively. Meptazinol (1-200 microM) increased the amplitudes of the indirect twitch tension in a dose-dependent manner. High concentrations of meptazinol (370 microM) reduced the twitch tension without the initial stimulation. The mean EC50 value of meptazinol-induced increase in twitch tension was 50 +/- 4.2 microM (n = 6). Morphine (2.9-290 microM) and fentanyl (2.9-290 microM) always reduced the amplitude of the twitch tension without initial stimulation. In the rat ileum, low concentrations of meptazinol (3.7-37 microM) increased the contractions produced by periarterial nerve stimulation, elicited at 10 or 20 Hz, in the presence of adrenergic blocking drugs, by 30%. Naloxone (1 microM) only partially reduced these contractions (by 25%), whereas atropine (1 microM) reduced these responses by 70%. Meptazinol (3.7 microM) increased the amplitude of the spontaneous contractions (by 50-100%) and sometimes this was accompanied by repetitive firing in the muscle. The twitch tension, in response to electrical field stimulation, was also increased by meptazinol (by 40-50%). At low concentrations, meptazinol produced no significant antagonism of applied ACh contracture, whereas at high concentrations, meptazinol (370 microM), morphine (29 microM) and fentanyl (29 microM) reduced the ACh response and shifted, to the right, the concentration-response curve, morphine being the most effective agent. Dose-ratios (test/control) of 100:4:2, with morphine, fentanyl and meptazinol, were obtained. Compared to meptazinol (relative potency = 1), morphine was 60 times as potent as meptazinol. Furthermore, the relative potency of meptazinol did not significantly change in the presence of naloxone, whereas those of morphine and fentanyl were changed significantly (by a factor of 10 and 2 respectively). These results showed that meptazinol, in low concentrations, may facilitate neuromuscular transmission, possibly via an increase in transmitter release. At high concentrations, meptazinol, like morphine and fentanyl, reduced the sensitivity of the post-junctional membrane to ACh. Furthermore, the blocking effect of meptazinol was only partially reduced by naloxone, and completely abolished by atropine in combination with naloxone. The latter effect may indicate a cholinergic mechanism in the action of meptazinol and that this may, in part, contribute to the analgesic effect of meptazinol.

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