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Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 354, Issue 5, pp 579–585 | Cite as

(±)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors

  • Miguel Reyes-Parada
  • Cecilia Scorza
  • Verónica Romero
  • Rodolfo Silveira
  • Jorge H. Medina
  • Danice Andrus
  • David E. Nichols
  • Bruce K. Cassels
Original Article

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 (4mg/kg), elicited significant hypothermia in mice. The affinity of the drug for 5-HT2A/2C receptors ([3H]ketanserin sites) was in the nanomolar range (Ki = 173 nM), whereas for 5-HT1A, benzodiazepine sites, and GABAA 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.

Key words

ALEPH-2 Serotonin receptor binding Anxiolytics Serotonin syndrome Phenylisopropylamines Rat Hypothermia Psychedelics 

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Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Miguel Reyes-Parada
    • 1
  • Cecilia Scorza
    • 1
  • Verónica Romero
    • 1
  • Rodolfo Silveira
    • 1
  • Jorge H. Medina
    • 2
  • Danice Andrus
    • 3
  • David E. Nichols
    • 3
  • Bruce K. Cassels
    • 4
  1. 1.Cell Biology DivisionInstituto de Investigaciones Biológicas Clemente EstableMontevideoUruguay
  2. 2.Instituto de Biologia CelularFacultad de MedicinaBuenos AiresArgentina
  3. 3.Department of Medicinal Chemistry and Molecular Pharmacology, Purdue UniversitySchool of Pharmacy and Pharmacal SciencesWest LafayetteUSA
  4. 4.Department of Chemistry, Faculty of SciencesUniversidad de ChileSantiagoChile

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