Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl-p-methoxyamphetamine derivatives
Abstract
The analgesic effects of (+)- and (-)-amphetamine (AMPH), (±)-p-methoxyamphetamine (MA), (±)-N-methyl-p-methoxyamphetamine (MMA) and (±)-N-ethyl-p-methoxyamphetamine (EMA) were compared using two different algesimetric tests in rats. In the formalin test, (+)-AMPH elicited significant antinociception at doses of 0.2, 2 and 8 mg/kg (i.p.); (-)-AMPH was active at 2 and 8 mg/kg, but not at 0.2 mg/kg; MA elicited very potent and long-lasting antinociception; MMA was less active than MA; EMA showed significant effects only at doses of 2 and 8 mg/kg. In the C-fiber evoked nociceptive reflex assay, i.v. (+)- and (-)-AMPH were ineffective, but the methoxy derivatives showed a similar pattern of action combining inhibitory and excitatory actions. To clarify apparent discrepancies between both algesimetric tests, some behavioral motor performance tests were carried out. These tests confirm the motor stimulatory properties of (+)-AMPH, not shared by the methoxylated amphetamine derivatives. The three methoxy derivatives elicited some stereotypies related to dopaminergic activation such as grooming behavior. (+)-AMPH was also the only drug to increase the acquisition of CARs while MA and EMA were without effect. Avoidance conditioning was seriously impaired in rats injected with MMA. This conditioned behavior can be related to the significant decrease of spontaneous motor activity observed with this drug. In conclusion, the introduction of a para-methoxy group strongly increases the analgesic effects of amphetamine without its stimulatory behavioral effects. The introduction of N-alkyl substituents decreases the analgesic potency of MA. © 2004 Elsevier Inc. All rights reserved.
Más información
Título según WOS: | Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl-p-methoxyamphetamine derivatives |
Título según SCOPUS: | Analgesic and behavioral effects of amphetamine enantiomers, p-methoxyamphetamine and n-alkyl-p-methoxyamphetamine derivatives |
Título de la Revista: | PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR |
Volumen: | 79 |
Número: | 2 |
Editorial: | PERGAMON-ELSEVIER SCIENCE LTD |
Fecha de publicación: | 2004 |
Página de inicio: | 199 |
Página final: | 212 |
Idioma: | English |
DOI: |
10.1016/j.pbb.2004.06.017 |
Notas: | ISI, SCOPUS |