NEUROPHARMACOLOGICAL PROFILE OF QUININE
NEUROPHARMACOLOGICAL PROFILE OF QUININE
No Thumbnail Available
Date
1989-03
Authors
AMABEOKU, GEORGE JIMBOYEKA
Journal Title
Journal ISSN
Volume Title
Publisher
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.
Description
A thesis submitted to the Postgraduate School, Ahmadu
Bello University, Zaria, in partial fulfilment of the
requirements for the degree of DOCTOR OF PHILOSOPHY.
DEPARTMENT OF PHARMACOLOGY AND CLINICAL PHARMACY,
FACULTY OF PHARMACEUTICAL SCIENCES,
AHMADU BELLO UNIVERSITY, ZARIA
March 1989
Keywords
NEUROPHARMACOLOGICAL,, QUININE