Rationale alpha-ET (alpha-ethyltryptamine), a homolog of the classical hallucinogen alpha-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 alpha-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the alpha-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of alpha-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-alpha-ET). Methods Rats were trained to discriminate alpha-ET (2.5 mg/kg) from saline using a two-lever operant task. Results The alpha-ET (ED50 = 1.04 mg/kg) stimulus generalized to MDMA (ED50 = 0.72 mg/kg) and MDA (ED50 = 0.48 mg/kg). The four alpha-ET derivatives produced various results; 4-OMe alpha-ET yielded negligible (20% maximum) alpha-ET-like responding; 5-OMe alpha-ET occasioned a modest level (40% maximum) of alpha-ET-like substitution; 6-OMe alpha-ET (ED50 = 6.26 mg/kg) generalized completely, but in a narrow dose range and in an inverted U-shaped manner; 7-OMe alpha-ET (ED50 = 2.78 mg/kg) generalized completely. Conclusions alpha-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, alpha-ET exerts a complex (compound) stimulus and appears to be a tryptamine counterpart of these prototypic phenylalkylamines. The monomethoxy analogs of alpha-ET produced an assortment of alpha-ET-like outcomes such that future investigations of these agents will likely need to be performed on an individual basis; extrapolations of alpha-ET-like effects to these analogs should be done judiciously.
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
Abate C.;
2024-01-01
Abstract
Rationale alpha-ET (alpha-ethyltryptamine), a homolog of the classical hallucinogen alpha-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 alpha-ET-like stimulus effects could be engendered by the prototypical phenylalkylamines MDMA ("Ecstasy") or MDA ("Love Drug") and (b) evaluate the alpha-ET-like stimulus effects of four synthesized aryl-substituted monomethoxy analogs of alpha-ET (4-OMe-, 5-OMe-, 6-OMe- and 7-OMe-alpha-ET). Methods Rats were trained to discriminate alpha-ET (2.5 mg/kg) from saline using a two-lever operant task. Results The alpha-ET (ED50 = 1.04 mg/kg) stimulus generalized to MDMA (ED50 = 0.72 mg/kg) and MDA (ED50 = 0.48 mg/kg). The four alpha-ET derivatives produced various results; 4-OMe alpha-ET yielded negligible (20% maximum) alpha-ET-like responding; 5-OMe alpha-ET occasioned a modest level (40% maximum) of alpha-ET-like substitution; 6-OMe alpha-ET (ED50 = 6.26 mg/kg) generalized completely, but in a narrow dose range and in an inverted U-shaped manner; 7-OMe alpha-ET (ED50 = 2.78 mg/kg) generalized completely. Conclusions alpha-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, alpha-ET exerts a complex (compound) stimulus and appears to be a tryptamine counterpart of these prototypic phenylalkylamines. The monomethoxy analogs of alpha-ET produced an assortment of alpha-ET-like outcomes such that future investigations of these agents will likely need to be performed on an individual basis; extrapolations of alpha-ET-like effects to these analogs should be done judiciously.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
