Behavioral and neurochemical pharmacology of six psychoactive substituted phenethylamines: mouse locomotion, rat drug discrimination and in vitro receptor and transporter binding and function.
Psychopharmacology (Berl)
; 231(5): 875-88, 2014 Mar.
Article
em En
| MEDLINE
| ID: mdl-24142203
ABSTRACT
RATIONALE Psychoactive-substituted phenethylamines 2,5-dimethoxy-4-chlorophenethylamine (2C-C); 2,5-dimethoxy-4-methylphenethylamine (2C-D); 2,5-dimethoxy-4-ethylphenethylamine (2C-E); 2,5-dimethoxy-4-iodophenethylamine (2C-I); 2,5-dimethoxy-4-ethylthiophenethylamine (2C-T-2); and 2,5-dimethoxy-4-chloroamphetamine (DOC) are used recreationally and may have deleterious side effects. OBJECTIVES:
This study compares the behavioral effects and the mechanisms of action of these substituted phenethylamines with those of hallucinogens and a stimulant.METHODS:
The effects of these compounds on mouse locomotor activity and in rats trained to discriminate dimethyltryptamine, (-)-DOM, (+)-LSD, (±)-MDMA, and S(+)-methamphetamine were assessed. Binding and functional activity of the phenethylamines at 5-HT1A, 5-HT2A, 5-HT2C receptors and monoamine transporters were assessed using cells heterologously expressing these proteins.RESULTS:
The phenethylamines depressed mouse locomotor activity, although 2C-D and 2C-E stimulated activity at low doses. The phenethylamines except 2C-T-2 fully substituted for at least one hallucinogenic training compound, but none fully substituted for (+)-methamphetamine. At 5-HT1A receptors, only 2C-T-2 and 2C-I were partial-to-full very low potency agonists. In 5-HT2A arachidonic acid release assays, the phenethylamines were partial to full agonists except 2C-I which was an antagonist. All compounds were full agonists at 5-HT2A and 5-HT2C receptor inositol phosphate assays. Only 2C-I had moderate affinity for, and very low potency at, the serotonin transporter.CONCLUSIONS:
The discriminative stimulus effects of 2C-C, 2C-D, 2C-E, 2C-I, and DOC were similar to those of several hallucinogens, but not methamphetamine. Additionally, the substituted phenethylamines were full agonists at 5-HT2A and 5-HT2C receptors, but for 2C-T-2, this was not sufficient to produce hallucinogen-like discriminative stimulus effects. Additionally, the 5-HT2A inositol phosphate pathway may be important in 2C-I's psychoactive properties.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fenetilaminas
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Psicotrópicos
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Receptores de Serotonina
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Discriminação Psicológica
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Proteínas Vesiculares de Transporte de Monoamina
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Atividade Motora
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article