Some correlations between local anesthetic-induced convulsions and gamma-aminobutyric acid in rat spinal cord.
The effects of local anesthetics (procaine and lidocaine) on the gamma-aminobutyric acid (GABA) and L-glutamic acid (Glu) levels in rat spinal cord were studied during the convulsive process. The present study also investigated the influence of central GABA manipulations on the local anesthetic-induced convulsions. An increase in spinal GABA levels was observed at the preconvulsive and convulsive states after administration of procaine (170 mg/kg, i.p.) or lidocaine (120 mg/kg, i.p.), which induced clonic convulsions; in the depressive state, GABA levels returned to normal; in all states, Glu levels were unchanged. Semicarbazide (25-100 mg/kg, i.p.), a glutamic acid decarboxylase inhibitor, produced a decrease in spinal GABA content and strongly enhanced both local anesthetic-induced convulsions as shown by a shortening of the latency and an increase in the mortality. Aminooxyacetic acid (AOAA; 10-40 mg-kg, i.p.), a GABA transaminase inhibitor, dose-dependently increased spinal GABA content and markedly suppressed procaine-induced convulsions. However, lidocaine-induced convulsions were enhanced by AOAA. These results suggest that the spinal GABA neuron may respond to the convulsions induced by local anesthetics. Furthermore, there is a clear relationship between spinal GABA content and procaine-induced, but not lidocaine-induced, convulsions.
Sawaki
K
K
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Ouchi
K
K
Sato
T
T
Kawaguchi
M
M
D000625:Aminooxyacetic Acid / Q000008:administration & dosage / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000032:analysis; D007274:Injections, Intraperitoneal; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011343:Procaine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced*; D012663:Semicarbazides / Q000008:administration & dosage / Q000494:pharmacology; D013116:Spinal Cord / Q000737:chemistry*; D005680:gamma-Aminobutyric Acid / Q000032:analysis*
D000779:Anesthetics, Local; D005971:Glutamates; D012663:Semicarbazides; D000625:Aminooxyacetic Acid; C010059:carbamylhydrazine; D011343:Procaine; D005680:gamma-Aminobutyric Acid; D008012:Lidocaine