( + )-1-(2,5-Dimethoxy+ethylthlophenyl )-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors
Serotonergic behavioral responses, efTects on motor activity and core temperature, and binding properties of the novel putative anxiolytic amphe!amine derivative (± )1-(2,5-dimethoxy-4-ethylthlophenyl)- 2-aminopropane (ALEPH-2), we~e examined in rodents in order to elucidate the mcchamsm lInderlying' its anxiolytic-Iike effect. After peripheral administration in rats, ALEPH-2 induced some symptoms of the serotonergic syndrome. e.g. forepaw treading ahd flat body posture. Additionally, a decrease in motor activity was observed. No significant efTects on the number of head shakes were observed after injection, although high inter-sllbject variability was noted. Higher doses of ALEPH-2, in the range exhibiting anxiolytic properties (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT 2Aí2C receptors (eH]ketanserin sites) was in the nanomolar range (K¡ = 173 nM), whereas for 5-HTIA, benzodiazepine sites, and GABAA receptors, the affinity was micromolar or lower. Based on these results the mechanism of action and the anxiolytic-Iike properties of ALEPH-2 are discussed.
This work was partially supported by CONIC'YT grant 94/038, International Foundation for Science (IFS), International Program in Chemical Sciences (IPICS), PEDECIBA (Uruguay), and NIH granl DA02189 (D.E.N.). M. Reyes-Parada was the recipient of a research fellowship from CONICYT (Uruguay). It was also partíally supported by FONDECYT grant N' 89/915 (Chile).
Quote ItemNaunyn-Schmiedeberg's Archives of Pharmacology, Vol. 354, Nº 5, p. 579-585, 1996.