Some correlations between procaine-induced convulsions and monoamines in the spinal cord of rats.
The relationships between the convulsions induced by the local anesthetic procaine and monoamines in the spinal cord were investigated in rats. The levels of dopamine (DA) and serotonin (5-HT) in the spinal cord were time-dependently increased after procaine (170 mg/kg, i.p.), which induced clonic convulsions, but the level of norepinephrine (NE) was unchanged. The rats that died during convulsions had a marked increase in DA. Phenobarbital (25 mg/kg, s.c.) produced both depletion of DA and elevation of 5-HT in the spinal cord and completely protected rats against convulsions. A 5-HT precursor, 5-hydroxytryptophan (5-HTP; 20-80 mg/kg, i.p.), suppressed the convulsions in a dose-dependent manner as shown by a decrease in the incidence and a prolongation of the latency, but a DA precursor, 3,4-dihydroxyphenylalanine (L-DOPA; 20-80 mg/kg, i.p.), markedly shortened the latency. Furthermore, the effect of L-DOPA on the convulsions was inhibited by the combination of 5-HTP. alpha-Methyl-p-tyrosine (20-80 mg/kg, i.p.) or DL-p-chlorophenylalanine (20-80 mg/kg, i.p.), an inhibitor of NE and DA or 5-HT biosynthesis, had a slight effect on the convulsions. These results suggest that procaine causes significant elevations of rat spinal DA and 5-HT in the convulsive process and suggest that dopaminergic and serotonergic neurons may be associated with procaine-induced convulsions.
Sawaki
K
K
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Kawaguchi
M
M
D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010634:Phenobarbital / Q000494:pharmacology; D011343:Procaine / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D013116:Spinal Cord / Q000187:drug effects*
D015306:Biogenic Monoamines; D011343:Procaine; D010634:Phenobarbital