Long-lasting ibogaine protection against NMDA-induced convulsions in mice.
Ibogaine, a putative antiaddictive drug, is remarkable in its apparent ability to downgrade withdrawal symptoms and drug craving for extended periods of time after a single dose. Ibogaine acts as a non-competitive NMDA receptor antagonist, while NMDA has been implicated in long lasting changes in neuronal function and in the physiological basis of drug addiction. The purpose of this study was to verify if persistent changes in NMDA receptors could be shown in vivo and in vitro after a single administration of ibogaine. The time course of ibogaine effects were examined on NMDA-induced seizures and [3H] MK-801 binding to cortical membranes in mice 30 min, 24, 48, and 72 h post treatment. Ibogaine (80 mg/kg, ip) was effective in inhibiting convulsions induced by NMDA at 24 and 72 hours post administration. Likewise, [3H] MK-801 binding was significantly decreased at 24 and 72 h post ibogaine. No significant differences from controls were found at 30 min or 48 h post ibogaine. This long lasting and complex pattern of modulation of NMDA receptors prompted by a single dose of ibogaine may be associated to its antiaddictive properties.
Leal
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MB
Departamento de Farmacologia, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
de Souza
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DO
Elisabetsky
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D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000493:pharmacokinetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D007050:Ibogaine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D007050:Ibogaine; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate