Some correlations between procaine-induced convulsions and monoamines in the spinal cord of rats.

Abstract

Abstract-The relationships between the convulsions induced by the local anes thetic 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-hydroxy tryptophan (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. a-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.

Effects of Anticonvulsants on Local Anaesthetic‐Induced Neurotoxicity in Rats

“…Phenobarbital binds to an allosteric regulatory site on the GABA-benzodiazepine receptor and enhances the GABA receptor-mediated current by prolonging the openings of the chloride channels (Porter & Meldrum 1992). Phenobarbital also produces a diminution of excitatory neurotransmitters in the CNS (Sawaki & Kawaguchi 1989). Carbamazepine acts on the same binding site of lidocaine in voltage-dependent sodium channels in the brain and prevents the development of lidocaine-induced seizures (Zimányi et al 1989).…”

“…Several investigators have pursued a functional role of central neurotransmitters in the control of local anaesthetics-induced convulsions. It has been demonstrated that local anaesthetics alter the neurotransmitter levels in the CNS during the convulsant process and their convulsions are modified by manipulation of the central neurotransmitters (Ciarlone & Juras 1981;Ikeda et al 1982;Sawaki & Kawaguchi 1989;Sawaki et al 1991;Yoshimura et al 1991;Abed 1994;Satoh et al 1996). However, the results obtained are not necessarily the same for all local anaesthetics.…”

Some Correlations between Local Anesthetic-Induced Convulsions and .GAMMA.-Aminobutyric Acid in Rat Spinal Cord.

“…Recently, we have found that the procaine convulsions are accompanied by significant in creases in spinal DA and 5-HT levels; the con vulsions are strongly suppressed by the 5-HT precursor 5-hydroxytryptophan and enhanced by the DA precursor 3,4-dihydroxyphenylala nine (15). These previous findings and the re sults obtained in this study suggest that the variations in spinal GABA content are not a causal factor for the convulsions induced by local anesthetics, but rather an endogenous anticonvulsant factor.…”

“…However, the spinal cord is one of the primary active sites in the motor functions and the neurotransmitters in the spinal cord as well as in the brain may be important in the local anesthetic-induced convulsive process. We recently demonstrated that significant elevations of DA and 5-HT levels in the spinal cord occur during the procaine-induced convulsive process (15).…”

Evaluation of high-performance liquid chromatography and mass spectrometry method for pharmacokinetic study of local anesthetic ropivacaine in plasma

“…These effects on the CNS are presumed to result from selective depression of inhibitory neurons and subsequent enhancement of the effect of excitatory neurons (19). A number of studies on the functional role of neurotransmitters in local anesthetic-induced convulsions have noted depression of neuronal activity (1,6,(14)(15)(16)(17)20) Laboratory studies on the toxicity of ropivacaine to the CNS in dogs noted that average dose and plasma concentration of ropivacaine at convulsive onset were 4.88 ± 0.47 mg/kg and 11.4 ± 0.9 μg/mL, animals were treated within the Guidelines for the Treatment of Experimental Animals approved by The Japanese Pharmacological Society and Tokyo Dental College.…”