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(±)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors
Keywords: temperature, behavior, disorder, acid, rat, mouse, animals, serotonin, antagonists, binding, assay, rats, mechanism, rodent, physiology, mice, metabolism, site, experiment, male, receptor, motor, agents, sites, amphetamine, agent, body, dose, drug, hypothermia, article, antagonist, dose-response, variance, analysis, activity, ketanserin, anxiolytic, benzodiazepine, controlled, animal, study, 4, 8, 1, response, derivative, induced, of, intraperitoneal, administration, nonhuman, tranquilizing, Anti-Anxiety, Receptors,, GABA-A, Rats,, Wistar, 2, a, dipropylamino, hydroxytetralin, amiflamine, buspirone, cinanserin, muscimol, (2,5, dimethoxy, ethylthiophenyl), aminopropane, 1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane, 2,5, methylamphetamine, aminobutyric, chemically, effect, radioassay, 2,5-Dimethoxy-4-Methylamphetamine, Behavior,, Relationship,, Radioligand
Abstract
Serotonergic behavioral responses, effects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphetamine derivative (±)1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), were examined in rodents in order to elucidate the mechanism underlying its anxiolytic-like effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome, e.g. forepaw treading and flat body posture. Additionally, a decrease in motor activity was observed. No significant effects on the number of head shakes were observed after injection, although high inter-subject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4 mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT(2A/2C) receptors ([3H]ketanserin sites) was in the nanomolar range (K(i) = 173 nM), whereas for 5-HT(1A), benzodiazepine sites, and GABA(A) receptors, the affinity was micromolar or lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.
Más información
| Título de la Revista: | NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY |
| Volumen: | 354 |
| Número: | 5 |
| Editorial: | Springer |
| Fecha de publicación: | 1996 |
| Página de inicio: | 579 |
| Página final: | 585 |
| URL: | http://www.scopus.com/inward/record.url?eid=2-s2.0-0029658459&partnerID=q2rCbXpz |