Inhibition of Monoamine Neurotransmitter Transporters andCentral Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review

Dohi, Toshihiro; Kitayama, Shigeo; Morita, Kenichi; Sato, Tomoyuki; Arai, Shigeaki; Kumagai, Kozo; Hashimoto, Wataru; Kihira, Kenji

doi:10.2174/1568015023357888

Cited by 7 publications

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“…Data from the present and previous (Ref. 1) review. have shown that daily treatment with 2-PMPA provided protection against the development of seizure kindling by cocaine without altering the potency of the convulsion and convulsant thresholds.…”

Section: Othersmentioning

confidence: 91%

“…The evidence further supports the involvement of 5-HT 2C receptor-mediated mechanism in cocaine-induced convulsions through an inhibition of central serotonin transporters (SERT). Differences in pharmacological modification of cocaine-and local anesthetic-induced seizures have previously been discussed [1] and are summarized in Table 1 and Table 2.…”

Section: ) Acute Seizuresmentioning

confidence: 99%

“…Cocaine-and lidocaine-induced kindled seizures are enhanced 1) animals kindled with cocaine [32]. The data indicate that positive modulation of GABA A receptors is not a critical feature determining the ability of neurosteroids to prevent cocaine-kindling.…”

Section: Convulsions By Repeated Lidocaine Treatment (Lidocaine Kindlmentioning

confidence: 99%

“…Cocaine has two main pharmacological actions; inhibition of MAT including DAT, norepinephrine transporter (NET) and SERT and inhibition of Na + channels, while lidocaine possesses only the latter property. Comparing the ability of daily treatment with a subconvulsive dose of the following 3 local anesthetics with different properties; cocaine with a potent inhibitory action on MAT, meprylcaine with a relatively potent inhibitory action on MAT and lidocaine lacking an inhibitory effect on MAT [1], clearly showed that the two former local anesthetics produced kindling seizures within 5 days, while lidocaine did not. These results indicate that the chronic administration of local anesthetics that inhibit MAT can facilitate convulsive activity, while that of lidocaine, which lacks this property, does not [45].…”

Section: Convulsions By Repeated Lidocaine Treatment (Lidocaine Kindlmentioning

confidence: 99%

“…In this update paper, we further summarize a recent progress on our previous review [1], accompanying with summary of influences of several drugs on cocaine-induced seizures in comparison with those on synthetic local anesthet *Address correspondence to this author at the Department of Dental Pharmacology, Division of Integrated Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan; Tel: +81-82-257-5640; Fax: +81-82-257-5644; E-mail: todohi@hiroshima-u.ac.jp ics-induced seizures and illustration of molecular basis of structure-function relationship of MAT, a critical target molecule for cocaine to produce central stimulation.…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of Monoamine Neurotransmitter Transporters and Central Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review-Update

Dohi¹,

Kitayama²,

Morita³

2005

CMCCNSA

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Monoamine transporters (MAT) are the target molecules of cocaine for induction of its central stimulating effect, resultant reward. Sensitization of central nervous system stimulation by cocaine is produced by intermittent use of cocaine and typically appears in behavioral hyperactivity in animals. Na + channels are other important molecules for induction of seizures of cocaine in abuse. The mechanisms for the expression of seizures and development of cocaine kindling by repeated cocaine intake may include the facilitation by inhibition of MAT of seizures induced by γ-aminobutyric acid obstacle-related mechanism resulting from an inhibition of Na + channels on the nerve by cocaine.Various molecular biological techniques have been utilized to investigate the structure-function relationship of MAT molecules and revealed multiple molecular determinates on MAT molecules for critical interaction with cocaine. The evidence would help to understand the molecular interaction of MAT and cocaine, leading to the development of medication for cocaine reward and kindling.

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Section: Othersmentioning

confidence: 91%

Section: ) Acute Seizuresmentioning

confidence: 99%

Section: Convulsions By Repeated Lidocaine Treatment (Lidocaine Kindlmentioning

confidence: 99%

Section: Convulsions By Repeated Lidocaine Treatment (Lidocaine Kindlmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Inhibition of Monoamine Neurotransmitter Transporters and Central Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review-Update

Dohi¹,

Kitayama²,

Morita³

2005

CMCCNSA

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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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Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics

et al. 2006

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Alterations of norepinephrine transporter (NET) function by chronic inhibition of NET in relation to sensitization to seizures induce by cocaine and local anesthetics were studied in mice. Daily administration of desipramine, an inhibitor of the NET, for 5 days decreased [(3)H]norepinephrine uptake in the P2 fractions of hippocampus but not cortex, striatum or amygdalae. Co-administration of lidocaine, bupivacaine or tricaine with desipramine reversed this effect. Daily treatment of cocaine increased [(3)H]norepinephrine uptake into the hippocampus. Daily administration of desipramine increased the incidence of appearance of lidocaine-induced convulsions and decreased that of cocaine-induced convulsions. Co-administration of lidocaine with desipramine reversed the changes of convulsive activity of lidocaine and cocaine induced by repeated administration of desipramine. These results suggest that down-regulation of hippocampal NET induced by chronic administration of desipramine may be relevant to desipramine-induced sensitization of lidocaine convulsions. Inhibition of Na(+) channels by local anesthetics may regulate desipramine-induced down-regulation of NET function. Repeated administration of cocaine induces up-regulation of hippocampal NET function. Desipramine-induced sensitization of lidocaine seizures may have a mechanism distinct from kindling resulting from repeated administration of cocaine.

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Inhibition of Monoamine Neurotransmitter Transporters andCentral Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review

Cited by 7 publications

References 0 publications

Inhibition of Monoamine Neurotransmitter Transporters and Central Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review-Update

Inhibition of Monoamine Neurotransmitter Transporters and Central Nervous System Stimulation Induced by Synthetic Local Anesthetics and Cocaine: A Comparative Review-Update

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

Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics

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