Pharmacologic analysis of non-synonymous coding 5-HT2A SNPs reveals alterations psychedelic drug potencies and efficacies
Gavin P. Schmitz, Manish K. Jain, Samuel T. Slocum, Bryan L. Roth
bioRxiv Preprint Server December 9, 2021 preprint DOI: 10.1101/2021.12.09.472000 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro pharmacological study |
|---|---|
| Population | Seven non-synonymous single nucleotide polymorphisms of the 5-HT2A serotonin receptor |
| Key points | Non-synonymous SNPs in the 5-HT2A receptor exert drug-specific, modest but statistically significant effects on the efficacy and potency of four psychedelic drugs. |
Abstract
Serotonin (5-Hydroxytryptamine; 5-HT) 2A receptor (5-HT2AR) signaling is essential for the actions of classical psychedelic drugs. In this study, we examined whether random sequence variations in the gene (single nucleotide polymorphisms, SNPs) encoding the 5-HT2AR affect the signaling of four commonly used psychedelic drugs. We examined the in vitro pharmacology of seven non-synonymous SNPs, which give rise to S12N, T25N, D48N, I197V, A230T, A447V, and H452Y variant 5-HT2A serotonin receptors. We found that these non-synonymous SNPs exert statistically significant, although modest, effects on the efficacy and potency of four therapeutically relevant hallucinogens. Significantly, the in vitro pharmacological effects of the SNPs drug actions at 5-HT2AR are drug specific.