Serotonin 1A Receptors Modulate Serotonin 2A Receptor-Mediated Behavioral Effects of 5-Methoxy-,-dimethyltryptamine Analogs in Mice.

5-methoxy-,-dimethyltrytpamine (5-MeO-DMT) analogs are used as recreational drugs, but they are also being developed as potential medicines, warranting further investigation into their pharmacology. Here, we investigated the neuropharmacology of 5-MeO-DMT and several of its -alkyl, -allyl, and 2-methyl analogs, with three major aims: 1) to determine in vitro receptor profiles for the compounds, 2) to characterize in vitro functional activities at serotonin (5-HT) 2A receptors (5-HT) and 1A receptors (5-HT), and 3) to examine the influence of 5-HT on 5-HT-mediated psychedelic-like effects in the mouse head twitch response (HTR) model. In vitro receptor binding and functional assays showed that all 5-MeO-DMT analogs bind with high affinity and activate multiple targets (e.

mGlu and mGlu receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats.

Rationale: The subjective effects of alcohol are associated with alcohol use disorder (AUD) vulnerability and treatment outcomes. The interoceptive effects of alcohol are part of these subjective effects and can be measured in animal models using drug discrimination procedures. The newly developed mGlu and mGlu negative allosteric modulators (NAMs) are potential therapeutics for AUD and may alter interoceptive sensitivity to alcohol.

Structure-activity relationships for locomotor stimulant effects and monoamine transporter interactions of substituted amphetamines and cathinones.

Substitutions to the phenethylamine structure give rise to numerous amphetamines and cathinones, contributing to an ever-growing number of abused novel psychoactive substances. Understanding how various substitutions affect the pharmacology of phenethylamines may help lawmakers and scientists predict the effects of newly emerging drugs. Here, we established structure-activity relationships for locomotor stimulant and monoamine transporter effects of 12 phenethylamines with combinations of para-chloro, β-keto, N-methyl, or N-ethyl additions.

Distinct Effects of Methamphetamine Isomers on Limbic Norepinephrine and Dopamine Transmission in the Rat Brain.

Methamphetamine (METH) is a psychostimulant that primarily exerts its effects on the catecholamine (dopamine (DA) and norepinephrine (NE)) systems, which are implicated in drug addiction. METH exists as two distinct enantiomers, dextrorotatory (d) and levorotatory (l). In contrast to d-METH, the major component of illicit METH used to induce states of euphoria and alertness, l-METH is available without prescription as a nasal decongestant and has been highlighted as a potential agonist replacement therapy to treat stimulant use disorder.