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

Toshihiro      Dohi; Shigeo      Kitayama; Katsuya      Morita

Abstract

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.

Keywords: cocaine, local anesthetic, transporter, dopamine, reward, kindling

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