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

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-ethylthio-phenyl)-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 of lower. Based on these results the mechanism of action and the anxiolytic-like properties of ALEPH-2 are discussed.

• Authors: M Reyes-Parada, C Scorza, V Romero, R Silveira, J H Medina, D Andrus, D E Nichols, B K Cassels
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 354 Issue 5 Pg. 579-85 (Nov 1996) ISSN: 0028-1298 [Print] Germany
• PMID: 8938655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Anxiety Agents
• Receptors, GABA-A
• Receptors, Serotonin
• Serotonin Antagonists
• 2,5-Dimethoxy-4-Methylamphetamine
• Ketanserin
• 1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane

Topics

• 2,5-Dimethoxy-4-Methylamphetamine (administration & dosage, analogs & derivatives, metabolism, pharmacology)
• Analysis of Variance
• Animals
• Anti-Anxiety Agents (administration & dosage, metabolism, pharmacology)
• Behavior, Animal (drug effects)
• Binding Sites
• Body Temperature (drug effects)
• Dose-Response Relationship, Drug
• Hypothermia (chemically induced)
• Ketanserin (metabolism)
• Male
• Mice
• Motor Activity (drug effects)
• Radioligand Assay
• Rats
• Rats, Wistar
• Receptors, GABA-A (metabolism, physiology)
• Receptors, Serotonin (metabolism, physiology)
• Serotonin Antagonists (metabolism)