Author Topic: ALEPH-2 as an anxiolytic?  (Read 3405 times)

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ALEPH-2 as an anxiolytic?
« on: August 18, 2003, 08:58:00 AM »
ALEPH-2, the amphetamine counterpart of 2C-T-2, has been found to have anxiolytic properties, but neuroscientists are at a loss when it comes to explain why. It should however be noted that the rats are recieving 10-100 times the dosage reccommended by Shulgin in

Pihkal #4


Behavioral Effects of the Putative Anxiolytic (±)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) in Rats and Mice
M. C. Scorza, M. Reyes-Parada, R. Silveira, et. al.

Pharmacology Biochemistry and Behavior, 54(2), 355-361 (1996)



Behavioral effects of the phenethylamine derivative (±)-1-(2,5-dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2) were studied in mice and rats. Murine locomotor activity, measured with a photocell actometer, was markedly depressed following IP injection of 2 and 6 mg/kg of the drug. The same doses of the drug also decreased frequency and duration of head dipping and the number of rearings in the hole board apparatus. In the murine elevated plus maze 2 and 6 mg/kg of ALEPH-2 increased the percentage of both open arm entries and time. The total number of entries into the enclosed arms was not significantly affected by the drug. In the rat, 2-12 mg/kg ALEPH-2, IP, decreased photobeam counts in the actometer in a dose-dependent fashion. Both 2 and 4 mg/kg of the drug increased the percentage of open arm entries, but only the highest dose significantly increased the percentage of time spent on the open arms. The dose of 4 mg/kg ALEPH-2 also significantly decreased the total number of enclosed arm entries. Finally, in a recently developed model of anxiety and memory, the elevated T-maze, the doses of 2 and 4 mg/kg ALEPH-2 did not change inhibitory avoidance of the open arms. Nevertheless, the highest dose had an amnestic effect on this task, repeated 72 h later in the absence of drug. In addition, this dose significantly increased the latency to escape from the open arms and had an amnestic effect measured 72 h later. Overall, these results indicate that ALEPH-2 possesses anxiolytic, amnestic as well as sedative and/or motor depressant actions.

(±)-1-(2,5-Dimethoxy-4-ethylthiophenyl)-2-aminopropane (ALEPH-2), a novel putative anxiolytic agent lacking affinity for benzodiazepine sites and 5-HT1A receptors
M. Reyes-Parada, C. Scorza, V. Romero, R. Silveira, J. H. Medina, D. Andrus, D. E. Nichols, B. K. Cassels

Naunyn-Schmiedeberg's Arch Pharmacol 354, 579-585 (1996)



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-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.


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Another ALEPH-2 Article
« Reply #1 on: May 08, 2004, 01:37:00 PM »
ALEPH-2, a suspected anxiolytic and putative hallucinogenic phenylisopropylamine derivative, is a 5-HT2a and 5-HT2c receptor agonist
Acuña-Castillo, C.; Scorza, c.; Reyes-Parada, M.; Cassels, BK.; Huidobro-Toro, JP.
Life Sciences 67 (2000) 3241–3247


To assess the pharmacodynamic profile of ALEPH-2, a phenylisopropylamine derivative with alleged anxiolytic and hallucinogenic properties, Xenopus laevis oocytes were microinjected with either of the rat cRNA for the 5-HT2A or the 5-HT2C receptor. Concentration-response curves were obtained following the exposure of the oocytes to varying concentrations of either ALEPH-2 or 5-hydroxytryptamine (5-HT) for 10 s. ALEPH-2 is a partial agonist on the 5-HT2A receptor with a similar potency to 5-HT. In contrast, ALEPH-2 is a full 5-HT2C receptor agonist and is about 15-fold less potent than 5-HT. Pre-application of 1µM ritanserin antagonized the responses induced by 5-HT and ALEPH-2 to the same extent; however, the 5-HT2A receptor is more sensitive to ritanserin blockade than the 5-HT2C receptor.