Effects of 5-hydroxytryptophan, iproniazid and p-chlorophenylalanine on lidocaine seizure threshold of mice

Oliveira, Luiz Fernando de; Bretas, A.D.

doi:10.1016/0014-2999(74)90162-9

Cited by 14 publications

(4 citation statements)

References 14 publications

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“…On the contrary, 5-HT 2 receptor antagonists antagonized cocaine-induced convulsions [21,24,26]. An increase in brain content of 5-HT also intensified convulsions by local anesthetics, and a decrease in brain 5-HT content increased the threshold [1,4,5]. These results are consistent with the idea that an increase in serotonergic neuronal activity facilitates convulsive activity of both cocaine and local anesthetics.…”

Section: Introductionsupporting

confidence: 70%

Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities

et al. 2005

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The present study examined whether the inhibition of serotonin transporters (SERT) contributes to cocaine- and other local anesthetics-induced convulsions, and which subtypes of 5-HT receptor are involved in the convulsions. For this purpose, cocaine, meprylcaine and lidocaine, all of which have different effects on SERT, were used as convulsants and the effects of serotonin reuptake inhibitors (SSRIs), specific agonists and antagonists for 5-HT receptor subtypes were evaluated in mice. Administration of SSRI, zimelidine, citalopram and fluoxetine, 5-HT(2A,2C) receptor agonist, R(-)-DOI and the 5-HT2C receptor agonists, mCPP, and MK212 resulted in a marked increase in incidence of convulsions and a reduction in the threshold of lidocaine-induced convulsions, while the 5-HT2B receptor agonist, BW723C86, had little influence. On the other hand, SSRI did not affect the measured parameters in meprylcaine- and cocaine-induced convulsions. R(-)-DOI, mCPP, and MK212 reduced the threshold of meprylcaine or cocaine with less extent than the reduction of lidocaine threshold. Incidence of cocaine- and meprylcaine-induced convulsions was significantly reduced by 5-HT(2A,2B,2C) antagonist, LY-53857, and 5-HT2C antagonist, RS 102221. The threshold of cocaine and meprylcaine was significantly increased by both antagonists. 5-HT2A antagonists MDL 11,939 and ketanserin, and 5-HT2B antagonist SB 204741 except at high doses had little effect on cocaine- and meprylcaine-induced convulsions. None of these antagonists altered the parameters of lidocaine-induced convulsions. Pretreatment with fluoxetine but not citalopram increased the plasma concentration of lidocaine. These results suggest that the increase of serotonergic neuronal activity through 5-HT2C receptor stimulation was responsible for increased activity of local anesthetics-induced convulsions and support the involvement of this mechanism in cocaine- and meprylcaine- but not in lidocaine-induced convulsions through their direct inhibitory action on central SERT.

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Section: Introductionsupporting

confidence: 70%

Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities

et al. 2005

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“…On the other hand, there were few studies on the re lationship between local anesthetic-induced convulsions and brain amines. It has been sug gested that endogenous brain stores of 5-HT may play role in the CNS toxicity of local anesthetics because an increase in brain con tent of 5-HT intensified local anesthetic-in duced convulsions, while a decrease in 5-HT content increased the threshold (18,19). Ciar lone reported that DA depletion lowered lido caine and procaine-induced seizure thresholds (20), while concurrent depletion of brain NA and DA had no effect on lidocaine seizure threshold (21).…”

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confidence: 99%

Changes in Convulsion Susceptibility of Lidocaine by Alteration of Brain Catecholaminergic Functions.

et al. 1991

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Influences of the manipulation of brain catecholaminergic neuronal activity on the incidence of lidocaine-induced convulsions in mice were studied and compared with those of pentylenetetrazol (PTZ)-induced convulsions. a-Methyl-p tyrosine (a-MPT) decreased both brain noradrenaline (NA) and dopamine (DA) levels, and disulfiram decreased the NA level and increased the DA level. The inci dence of lidocaine-induced convulsions was decreased by treatments with a -MPT and disulfiram, while that of PTZ was increased by either treatment. The incidence of lidocaine-induced convulsions was slightly, but not significantly increased by L-dihy droxyphenylalanine (L-DOPA), although the brain DA level was increased by L DOPA. Methamphetamine and desipramine increased the incidences of lidocaine induced convulsions. These results may suggest that brain catecholaminergic neurons, differing from their role in inhibiting control of PTZ-seizure, act to facilitate lidocaine-induced convulsions.A major pharmacological sign of toxicity from local anesthetic administration is an ex citation of the central nervous system (CNS) as in the development of general tonic-clonic convulsions, although local anesthetics have an anticonvulsant effect in low doses (1). In travenously infused lidocaine has been shown to cause a tetraphasic action on CNS electrical activity (initially a decrease; secondarily, an increase and then decrease; and finally, an in crease in reticular neruonal firing) in cats (2). Stimulation of the CNS by local anesthetics is characterized by the activation of limbic dis charges which is most striking in the amygda loid nuclear complex (3-6) and the increase in metabolic activity which is notable in the hippocampus (7). It is generally agreed that local anesthetics induce convulsions by de pressing inhibitory neurons, thereby permit ting facilitation of excitatory neurons. This in terpretation is suggested by demonstrations that lidocaine blocked inhibitory synapses in rabbit cortical neurons, but had comparatively little effect on excitatory synapses (8), and that lidocaine facilitated the spinal monosyn aptic reflex, suggesting suppression of certain inhibitory spinal functions in preference to excitatory functions (9). y-Aminobutyric acid (GABA) is considered to be a major inhibi tory neurotransmitter in the mammalian CNS. We have demonstrated that local anesthetics inhibited GABA release from synaptosomes (10) and that intraventricularly administered

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“…Thus, several investigators began pursuing a possible correlation between local an esthetic induced convulsions and mono amines as inhibitory neurotransmitters in the CNS (3)(4)(5)(6)(7)(8)(9)(10)(11). However, the results obtained so far have been equivocal.…”

mentioning

confidence: 99%

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

Sawaki

Kawaguchi

1989

Jpn.J.Pharmacol

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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.

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Effects of 5-hydroxytryptophan, iproniazid and p-chlorophenylalanine on lidocaine seizure threshold of mice

Cited by 14 publications

References 14 publications

Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities

Inhibition of serotonin transporters by cocaine and meprylcaine through 5-TH2C receptor stimulation facilitates their seizure activities

Changes in Convulsion Susceptibility of Lidocaine by Alteration of Brain Catecholaminergic Functions.

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

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