Chloroquine-induced seizures in mice: the role of monoaminergic mechanisms.
The influence of some dopaminergic and noradrenergic agents on seizures induced by chloroquine (45-100 mg/kg, i.p.) was investigated in mice. Apomorphine (0.2-0.8 mg/kg, s.c.). L-dopa (25-50 mg/kg, s.c.) benserazide (5 mg/kg, i.p.) plus L-dopa (50 mg/kg, s.c.), pargyline (100 mg/kg, i.p.), FLA-63 (10-20 mg/kg, s.c.) and FLA-63 (10 mg/kg, s.c.) plus L-dopa (50 mg/kg, s.c.) profoundly shortened the latency of seizures induced by chloroquine (65 mg/kg, i.p.). L-Dopa (50 mg/kg, s.c.) weakly reduced the latency and weakly increased the incidence of chloroquine (50 mg/kg, i.p.)-induced seizures. alpha-Methyl-p-tyrosine (25-100 mg/kg, i.p.) dose-dependently and significantly reduced the incidence and significantly prolonged the latency of chloroquine (65 mg/kg, i.p.)-induced seizures. However, L-dopa (50 mg/kg, s.c.) effectively increased the proportion of animals convulsing and effectively reduced the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in alpha-methyl-p-tyrosine-pretreated mice. Haloperidol (0.25-1.0 mg/kg, i.p.) and pimozide (2-4 mg/kg, i.p.) markedly reduced the incidence and markedly prolonged the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in a dose-related manner. However, apomorphine (0.4-0.8 mg/kg, s.c.) and L-dopa (25-50 mg/kg, s.c.) profoundly attenuated the protective effects of haloperidol (0.5 mg/kg, i.p.) and pimozide (4 mg/kg, i.p.) against chloroquine (65 mg/kg, i.p.)-induced seizures.(ABSTRACT TRUNCATED AT 250 WORDS)
Amabeoku
G J
GJ
Department of Clinical Pharmacology, Medical School, University of Zimbabwe, Avondale, Harare.
Chikuni
O
O
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D002738:Chloroquine / Q000633:toxicity*; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D015306:Biogenic Monoamines; D002738:Chloroquine