NEUROPHARMACOLOGICAL PROFILE OF QUININE

NEUROPHARMACOLOGICAL PROFILE OF QUININE

Abstract:

The effects of quinine and the influence of various drugs were studied on locomotor and cataleptogenic activities, pentobarbitone-induced sleep, EEG and EMG, gross behaviour, analgesia, electroshock and leptazol – induced seizures and the levels of brain biogenic amines in mice, rats and young chicks. Low doses of quinine given intraperitoneally increased locomotor activity in mice while high doses reduced it. L-Dopa, benserazide and pargyline potentiated the effect of low dose of quinine on locomotor activity. DOPS did not alter the locomotor activity enhancing effect of quinine. However, -methy-p-tyrosine, pimozide, 1-sulpiride and SCH 23390 inhibited it. Pimozide inhibited locomotor activity enhancing effect of quinine in a manner similar to its antagonistic effect on that of d-amphetamine on locomotor activity. Quinine in moderate to high doses induced catalepsy in rats in a dose? related manner. Quinine shortened the onset and increased the intensity of pimozide-induced catalepsy. -Methyl-p-tyrosine effectively enhanced either quinine or pimozide-induced catalepsy. d-Amphetamine, on the other hand, attenuated the cataleptic effects produced by both quinine and pimozide. Moderate to high doses of quinine effectively shortened the onset and prolonged the duration of pentobarbitone-induced sleep in mice while low dose weakly delayed the onset and shortened the duration of pentobarbitoneX sleep. Pimozide and 1-sulpiride potentiated the enhancing effect of quinine on pentobarbitone-sleep while d-amphetamine attenuated it. Low dose of quinine desynchronizcd the EEG with activation of EMG and antagonized pentobarbitone – induced synchronization of EEG in young chicks. Although it desynchronized the EEG of the hyperstriatum, high dose of quinine profoundly reduced EMG activity and potentiated G synchronisation induced by pentobarbitone with marked reduction in EMG activity. Low doses of quinine induced stereotyped circling in mice with increase in locomotor activity: these effects decreased with increase in dose of quinine d-Amphetamineinduced stereotyped circling was weakly increased by low dose of quinine while high dose markedly reduced it. Pimozide, 1-sulpiride and SCH 23390 antagonized the stereotyped circling produced by either quinine in low dose or d-amphetamine. d-Amphetamine-induced desynchroniration of the EEG of young chicks was increased by low dose of quinine with profound increase in both reticular formation and EMG activities. High dose of quinine despite potentiating d—amphetamine – induced desynchronization of the EEG of the hyperstriatum,markedly reduced the activation of both reticular formation and EMG by d- arnphetamine. The dose dependent analgesia produced by quinine in moderate to high doses in mice was increased by pimozide. 1 – sulpiride and SCH 23390 while d-amphetamine attenuatedit. The analgesia induced by morphine in mice was significantly increased by both quinine and pimozide while d-amphetamine reduced it. Quinine, in all the doses used, did not protect the mice against electroshock seizure but in moderate to high doses protected the animals against leptazol-induced seizure. This anticonvulsant effect of quinine on leptazol induced seizure was increased by pimozide while d-amphetamine reduced it. Low dose of quinine given intracerebroventricularly produced similar effect on gross behaviour to that of apomorphine and dopamine which are known to have well established central effects. These results correlate well with that obtained with quinine in low dose given intraperitoneally. The hyperactivity induced by icv quinine, apomorphine and dopamine was attenuated by pimozide while propranolol did not alter it. The results obtained from the high performance liquid chromatographic analysis revealed a differential effect of quinine on the monoamine and indole metabolism in the various regions of the brain. It is not surprising that the distribution of dopamine in differnet brain regions of rats pretreated with quinine followed the same pattern as that of endogenous dopamine in control rats. The biochemical data correlate with the behavioural change elicited by quinine.

NEUROPHARMACOLOGICAL PROFILE OF QUININE