Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by modification of monoamines in rat brain.
The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.
Satoh
T
T
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Sawaki
K
K
Kawaguchi
M
M
D018663:Adrenergic Agents / Q000494:pharmacology; D000779:Anesthetics, Local / Q000633:toxicity*; D000818:Animals; D001565:Benzoates / Q000633:toxicity*; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000494:pharmacology
D018663:Adrenergic Agents; D000779:Anesthetics, Local; D001565:Benzoates; D015306:Biogenic Monoamines; D015259:Dopamine Agents; D018490:Serotonin Agents; C105695:tolycaine; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine