The Central Effects of Xylopinine in Mice

Abstract

The depression of the spontaneous movement of mice by xylopinine, 2,3,10,11-tetra methoxy-5,6-13a-tetrahydro-8-dibenzo(a-g)quinolizinc, has been reported by Nakanishi (1). In the unanesthetized rabbit, the intravenous injection of xylopinine produced high voltage slow waves and increased spindle waves in EEG. The threshold voltage for eliciting the reticular arousal response by stimulation of the ascending reticular formation was also elevated.Recently, Hsu and Kin (2) have studied the pharmacological effects of tetrahydro palmatine and its analogues. They showed that tetrahydropalmatine exerted sedative tranquilizing effects in mice.The present experiments were designed to study sedative-tranquilizing effects of xylopinine in mice. METHODSThe experiments were performed in the mice, weighing 14 to 18 g, of both sexes.The drugs used in this experiment were all injected intraperitoneally in 0.2 ml of aqueous solution per 10 g. The drugs used were xylopinine citrate, tetrabenazine hy drochloride, chlorpromazine hydrochloride, methamphetamine hydrochloride, trans-dl 2-phenylcyclopropylamine maleate (SKF-385), caffeine and amobarbital sodium. Because of less solubility in water SKF-385 was suspended in the physiological saline solution.The locomotor movement of mice was measured as a number of rotations of the rotation apparatus devised by Takagi et al. (3). The sleeping time of mice was deter mined by measuring the period of time of the disappearance of the righting reflex over 20 seconds and was expressed in minutes. The antagonistic effects of xylopinine were assayed on the lethality in mice due to seizures produced by the injection of the convulsive drugs and by the electroshock. For the induction of the electroshock seizure the apparatus of Woodbury and Davenport (4) was used. Further details of the ex perimental methods will be described under the RESULTS. RESULTSI. Effects of vylopinine on the motor movement of the unanesthetized mice When the mice were transferred from the feeding cage to the rotation apparatus in the daytime, the animals showed the exploratory movements for a while, and some

ELECTROENCEPHALOGRAPHIC STUDIES OF XYLOPININE, 2,3,10,11-TETR AMETHOX Y-5,6-13,13a-TETRAH YDRO-8-DIBENZO(a-g) QUINOLIZINE CITRATE IN RABBIT

“…Though the antagonism between methamphetamine and xylopinine was not proved in the spon taneous EEG, it was demonstrated in the recruiting response. This antagonism have some relation with the antagonistic action of xylopinine against the convulsion and lethality of methamphetamine in mice, shown by Yamamoto (2). Further, it is worth to mention that the depressive effect of xylopinine markedly manifests in the hi.ppo campus where is the site of rich distribution of noradrenaline and monoamine oxidase.…”

“…However, the large doses elevated the stimulation threshold. The decrease of the threshold for the seizure by large dose have some relation with the fact that the threshold for the maximal extensor seizure produced by electroshock was decreased by xylopinine (2).…”

“…Nakanishi (1) and Yamamoto (2) showed that the pharmacological effects of xylopinine resembled to those of chlorpromazine in the following points: 1) sedation and hypotension of central origin, 2) peripheral adrenolytic and sympatholytic effects , 3) potentiation on barbiturate sleep, 4) antagonism against central effects of metham phetamine and 5) no significant effect on metabolism of tissue noradrenaline. The signi ficant difference between tetrabenazine and xylopinine suggests that the former exerts the pharmacological effects through depletion of the brain noradrenaline , while the latter does so by competing the receptor binding with noradrenaline as in case of chlorpro mazine (3).…”

“…Xylopinine citrate, diluted appropriately from 1% stock solution of saline, was in jected into the marginal ear vein after 1% solution of lidocaine hydrochloride was ap plied at the site of injection. The dose range from I to 10 mg/kg was selected in references with the pharmacological effects of xylopinine in mice, cats and rabbits in the previous reports (1,2). Other drugs used were adrenaline hydrochloride, methamphetamine hydro chloride, trans-dl-phenylcyclopropylamine maleate (SKF-385), hexamethonium bitartrate and lidocaine hydrochloride.…”

“…The pharmacological effects of xylopinine (2,3,10,11-tetramethoxy-5,6-13,13a-tetra hydro-8-dibenzo(a-g)quinolizine) in rabbit, cat and dog have been reported elsewhere (1,2). Xylopinine induced a long-lasting fall of blood pressure and peripheral adreno lytic and sympatholytic effects.…”