(+/-)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and serotonin-1A receptors.
M Reyes-Parada, C Scorza, V Romero, R Silveira, J H Medina, D Andrus, D E Nichols, B K Cassels
Naunyn-Schmiedeberg's archives of pharmacology November 1, 1996 DOI: 10.1007/bf00170831 via PubMed
Summary
The novel amphetamine derivative ALEPH-2, a putative anxiolytic, produced serotonergic syndrome symptoms like forepaw treading and flat body posture in rats, along with decreased motor activity. No significant effect on head shakes was observed, though variability was high. In mice, higher doses (4 mg/kg) caused significant hypothermia. The drug showed nanomolar affinity for 5-HT2A/2C receptors (Ki = 173 nM) but only micromolar or lower affinity for 5-HT1A, benzodiazepine, and GABAA receptors. These findings suggest ALEPH-2's anxiolytic-like effects involve serotonergic mechanisms, particularly 5-HT2A/2C receptor interactions.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rodents (rats and mice) |
| Citations | 6 |
| Key finding | ALEPH-2 induces serotonergic syndrome symptoms and hypothermia, and binds with nanomolar affinity to 5-HT2A/2C receptors, suggesting its anxiolytic-like effects are mediated through these 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.