[35S]GTPγS (Guanosine-5′-O-(γ-thio)triphosphate-[35S]) Binding Scintillation Proximity Assay Experiments in Postmortem Brain Tissue

Muneta-Arrate, Itziar; Dı́ez-Alarcia, Rebeca

doi:10.1007/978-1-0716-3307-6_3

Methods in Molecular Biology

2023

DOI: 10.1007/978-1-0716-3307-6_3

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[35S]GTPγS (Guanosine-5′-O-(γ-thio)triphosphate-[35S]) Binding Scintillation Proximity Assay Experiments in Postmortem Brain Tissue

Itziar Muneta-Arrate

Rebeca Dı́ez-Alarcia

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2024

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The selective 5-HT_2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

Jensen,

Cecchi,

Hibicke

et al. 2024

Preprint

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Psychedelic-assisted psychotherapy has over the last decade emerged as a promising treatment strategy for mental health disease, and the therapeutic potential in classical psychedelics such as psilocybin, LSD and 5-MeO-DMT is presently being pursued in a plethora of clinical trials. However, the resurgent interest in the drugs as therapeutics has also prompted a search for novel agents with more specific pharmacological activities than the rather promiscuous classical psychedelics. Here we present the results of an elaborate preclinical characterization of one such compound, LPH-5 [(S)-3-(2,5-dimethoxy-4-(trifluoromethyl)phenyl)piperidine]. LPH-5 was found to be a potent partial agonist at the 5-HT2A receptor (5-HT2AR) and to exhibit pronounced selectivity for this receptor over the related 5-HT2B and 5-HT2C receptors in a range of functional assays. LPH-5 (0.375 - 12.0 mg/kg, i.p.) dose-dependently induced head-twitch responses (HTR) in Sprague Dawley rats, with substantial 5-HT2AR engagement being observed at 0.5-1.0 mg/kg. Acute administration of LPH-5 (1.5 mg/kg, i.p.) induced robust antidepressant-like effects in Flinders Sensitive Line rats and adrenocorticotropic hormone-treated Sprague Dawley rats, and LPH-5 (0.3 and 1.5 mg/kg, i.p.) induced significant effects in a recently developed Wistar Kyoto rat model proposed to reflect the long-term antidepressant-like effects produced by psychedelics in humans. In conclusion, selective 5-HT2AR activation, as mediated here by LPH-5, seems to hold antidepressant potential, suggesting that this activity component is key for the beneficial effects of classical psychedelics. Hence, we propose that LPH-5 and other 5-HT2AR-selective agonists could hold potential as therapeutics in psychiatric disease as a new generation of psychedelic-derived antidepressant.

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The selective 5-HT_2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

Jensen,

Cecchi,

Hibicke

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

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[35S]GTPγS (Guanosine-5′-O-(γ-thio)triphosphate-[35S]) Binding Scintillation Proximity Assay Experiments in Postmortem Brain Tissue

Cited by 1 publication

References 16 publications

The selective 5-HT_2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

The selective 5-HT_2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

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[35S]GTPγS (Guanosine-5′-O-(γ-thio)triphosphate-[35S]) Binding Scintillation Proximity Assay Experiments in Postmortem Brain Tissue

Cited by 1 publication

References 16 publications

The selective 5-HT2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

The selective 5-HT2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

Contact Info

Product

Resources

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The selective 5-HT_2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents

The selective 5-HT_2Areceptor agonist LPH-5 induces persistent and robust antidepressant-like effects in rodents