Discriminative stimulus properties of α-ethyltryptamine (α-ET) in rats: α-ET-like effects of MDMA, MDA and aryl-monomethoxy substituted derivatives of α-ET.

Autor: Abate C; Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 800 E. Leigh St., STE 205, Richmond, VA, 23219-0540, USA.; Department of Pharmacy-Pharmaceutical Sciences, University of Bari 'Aldo Moro', Via E. Orabona, 4, Bari, I-70125, Italy., Young R; Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 800 E. Leigh St., STE 205, Richmond, VA, 23219-0540, USA. ryoung@vcu.edu., Dukat M; Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 800 E. Leigh St., STE 205, Richmond, VA, 23219-0540, USA., Glennon RA; Department of Medicinal Chemistry, School of Pharmacy, Medical College of Virginia Campus, Virginia Commonwealth University, 800 E. Leigh St., STE 205, Richmond, VA, 23219-0540, USA.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2024 Dec 28. Date of Electronic Publication: 2024 Dec 28.
DOI: 10.1007/s00213-024-06738-y
Abstrakt: Rationale α-ET (α-ethyltryptamine), a homolog of the classical hallucinogen α-methyltryptamine, was once prescribed clinically as an antidepressant. Classical psychedelic drugs are currently of interest as potential pharmacotherapy for psychiatric disorders. Objectives Drug discrimination was used to (a) determine if α-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the α-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of α-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-α-ET). Methods Rats were trained to discriminate α-ET (2.5 mg/kg) from saline using a two-lever operant task. Results The α-ET (ED 50  = 1.04 mg/kg) stimulus generalized to MDMA (ED 50  = 0.72 mg/kg) and MDA (ED 50  = 0.48 mg/kg). The four α-ET derivatives produced various results; 4-OMe α-ET yielded negligible (20% maximum) α-ET-like responding; 5-OMe α-ET occasioned a modest level (40% maximum) of α-ET-like substitution; 6-OMe α-ET (ED 50  = 6.26 mg/kg) generalized completely, but in a narrow dose range and in an inverted U-shaped manner; 7-OMe α-ET (ED 50  = 2.78 mg/kg) generalized completely. Conclusions α-ET stimulus effects are similar to those of MDMA, but appear more closely aligned to those of MDA and are produced by its stereoisomers which, when combined, exert MDA/MDMA-, hallucinogen- and some stimulant-like stimulus actions. Thus, α-ET exerts a complex (compound) stimulus and appears to be a tryptamine counterpart of these prototypic phenylalkylamines. The monomethoxy analogs of α-ET produced an assortment of α-ET-like outcomes such that future investigations of these agents will likely need to be performed on an individual basis; extrapolations of α-ET-like effects to these analogs should be done judiciously.
Competing Interests: Declarations. Ethical statement: The research reported here was reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) at Virginia Commonwealth University and is in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council 2011). Conflict of interest: On behalf of all authors, the corresponding author states that there is no conflict of interest.
(© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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