Molecular Psychiatry
March 14, 2024
Pol Puigseslloses, Gabriel Ketsela, Nicola Weiss et al.
23 citations
All tested 5-MeO-tryptamines selectively bind to 5-HT1A receptors over 5-HT2A receptors, with computational docking predicting better interaction in the 5-HT1A binding pocket. These compounds also interact with the serotonin transporter (SERT), where molecular size of the amino group influences affinity. 5-MeO-pyr-T acts as the most potent partial 5-HT releaser. All tryptamines elicit the head twitch response in mice, indicating potential hallucinogenic effects primarily mediated by 5-HT2A receptors, but 5-HT1A activation attenuates this response. Tryptamines producing stronger hypothermic responses via 5-HT1A tend to show lower hallucinogenic effects, highlighting opposing roles of the two receptors. Some compounds with low hallucinogenic effects remain potent 5-HT2A agonists, offering insight into non-hallucinogenic therapeutic ligands.
Frontiers in Psychiatry
October 3, 2022
Jordi Camarasa, Pol Puigseslloses, Edurne Urquizu et al.
5 citations
Conventional psychiatric drugs often fail due to limited efficacy, slow onset, or side effects. Psychoactive substances, historically used for spiritual and recreational purposes, have shown therapeutic potential for disorders like post-traumatic stress disorder and treatment-resistant depression when administered under medical supervision with psychotherapy. Drugs such as MDMA, ketamine, psilocybin, and LSD have yielded successful clinical outcomes. New psychoactive substances (NPS), including synthetic cathinones and tryptamines, despite their illicit use, expand the library of potential treatments, as many were originally synthesized for therapeutic aims. This review examines the evidence and properties needed for NPS to become viable therapeutic compounds.
Pharmaceuticals
June 15, 2011
Elena Escubedo, Sara Garcia-Ratés, Jordi Camarasa et al.
4 citations
Amphetamine derivatives like methamphetamine (METH) and MDMA (ecstasy) are neurotoxic in animal models and linked to cognitive impairments in heavy users. Their main targets are monoamine transporters, causing increased monoamine release. A key cause of neurotoxicity is increased production of reactive oxygen species (ROS). Blockade of α7 nicotinic acetylcholine receptors (nAChR) inhibits METH- and MDMA-induced ROS production in striatal synaptosomes, a process dependent on calcium and NO-synthase activation. α7 nAChR antagonists attenuated neurotoxicity in vivo, and memantine prevented cognitive impairment. MDMA acts as a partial agonist on α7 and an antagonist on heteromeric nAChR, with sustained calcium increases leading to calpain and caspase-3 activation.