Discriminative stimulus properties of a-ET...

[pHarmacist]

...optical isomers

Seoung-Soo Hong, Richard Young, Richard A. Glennon*
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, 410 N. 12th Street, Box 980540 VCU, 554A Smith Building, Richmond, VA 23298, USA

Received 15 March 2001; received in revised form 6 June 2001; accepted 29 June 2001

Abstract: a-Ethyltryptamine (a-ET) possesses central stimulant and hallucinogenic activity. Also, in tests of stimulus generalization using rats trained to discriminate the controlled substance analog (i.e., designer drug) N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) from vehicle, a-ET substituted for MDMA. These previous studies employed racemic a-ET. Because psychoactive phenylalkylamines with abuse potential can produce one or more of three distinct stimulus effects (i.e., amphetamine-, DOM- and/or PMMA-like effects) in animals trained to discriminate either the stimulant (+)amphetamine, the hallucinogen 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM), or N-methyl-1-(4-methoxyphenyl)-2-aminopropane (PMMA) from vehicle, and because these effects can be stereoselective, the individual optical isomers of a-ET were examined in groups of animals trained to discriminate (+)amphetamine, DOM, PMMA and MDMA from saline vehicle. (-)a-ET (ED 50 = 7.8 mg/kg), but not (+)a-ET (maximum of 53% drug-appropriate responding), substituted for (+)amphetamine, whereas (+)a-ET (ED 50 = 2.7 mg/kg), but not (-)a-ET (maximum of 33% drug- appropriate responding), substituted for DOM. Both optical isomers of a-ET substituted for PMMA and MDMA with ED 50 values of 1.6 and 1.4 mg/kg (PMMA-trained animals) and 1.3 and 2.0 mg/kg (MDMA-trained animals) for (-)a-ET and (+)a-ET, respectively. The results of this investigation suggest that both optical isomers of a-ET are capable of producing an MDMA/PMMA-like effect at nearly comparable doses, and that the stimulant or amphetamine-like nature of a-ET resides primarily with its (-)isomer whereas hallucinogenic or DOM-like character resides primarily with the (+)enantiomer.

D 2001 Elsevier Science Inc. All rights reserved.
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[pHarmacist]

TiHKAL: 5-MeO-a-ET is more potent than a-ET by a factor of two with 70 milligrams orally producing a trippy feeling that lasted several hours accompanied with an increased heart beat and difficulty in sleeping. There were no psychedelic effects as such, and no unpleasant side effects.

3-formyl-5-methoxy indole, I is prepared according to the method of Blaikee and Perkin, Soc. 125, 324, (1924)


2-(5-Methoxy-indolyl)-1-nitroethylene, II.

22.4 g. of ammonium acetate are mixed with 336 ccs. of nitromethane, the mixture is heated to 95 and 112 g. of 3-formyl-5-methoxy indole, I, are added. The heating is maintained for 20 minutes and a brown-orange precipitate is formed. The mixture is chilled and filtered and the crystals obtained are washed with nitromethane. After drying, 100 g. (72% of theoretical) of the desired product (m.p.= 161 celsius) are obtained. The product can be used as such in the following stage of the synthesis.

For analysis, the product is recrystallised from nitromethane and then from ethanol. A sample is obtained melting at 165 celsius. Compound II is in the form of brown-orange crystals which are soluble in alcohol and acetone, sparingly Analysis: C11H1,0,N, = 218.21.

Calculated: C 60.54% Found: C 60.6%

2-(5-Methoxy-indolyl)-1-nitrobutane, III.

An ether solution of ethyl magnesium iodide is prepared from 22.3 g. of magnesium, 162 g. of ethyl iodide and 375 ccs. of ether. 1.5 g. of cuprous chloride are added and the mixture agitated for 1 hour at 200 Celsius. 50 g. of compound II dissolved in 1,000 ccs. of anhydrous tetrahydrofuran are then added, with sufficient cooling to maintain the temperatures between 00 and 10 and in the course of the addition, a bright blue product crystallises out, becoming violet and at the end of the addition brown-red. The reaction mixture is agitated for some minutes at ambient temperature and cooled again. 750 ccs. of a 30% solution of ammonium chloride are then added and after agitation for 15 minutes the aqueous phase is decanted and extracted three times with ether. The ethereal solutions are combined and washed successively with ether, a 10% solution of sodium bisulphite and water. The solution is dried, filtered and evaporated to dryness in vacuo.

The residue after distillation is taken up in methylene chloride and after chilling 8.5 g. of compound II are separated by filtration.

Chromatography of the methylene chloride solution on 500 g. of alumina and elution with methylene chloride yields 4 fractions of ccs. which on distilling to dryness yield 24 g. of a very viscous brown-red oil comprising compound III.

Patent GB910992