Lysergic acid diethylamide stimulates cardiac human H2 histamine and cardiac human 5-HT4-serotonin receptors.
Ulrich Gergs, Hannes Jacob, Pauline Braekow, Britt Hofmann, Steffen Pockes, Laura J Humphrys, Uwe Kirchhefer, Charlotte Fehse, Joachim Neumann
Naunyn-Schmiedeberg's archives of pharmacology January 1, 2024 DOI: 10.1007/s00210-023-02591-6 via PubMed
Summary
AI-generated from the abstractLysergic acid diethylamide (LSD) increases the force and rate of heart contractions by activating two types of receptors: 5-HT4 serotonin receptors and H2 histamine receptors. In transgenic mouse hearts overexpressing human 5-HT4 or H2 receptors, LSD (up to 10 µM) increased contraction force and beating rate, effects blocked by specific antagonists (tropisetron for 5-HT4, cimetidine and GR 125487 for H2). In human atrial muscle strips from bypass surgery patients, LSD (10 µM) also increased contraction force after cilostamide pre-stimulation. These findings indicate LSD directly stimulates cardiac function through both receptor pathways.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Transgenic mice with cardiomyocyte-specific overexpression of human 5-HT4 or H2 receptors, and human right atrial tissue from bypass surgery patients |
| Intervention | LSD |
| Dose | up to 10 µM |
| Topics | LSD |
| Keywords | Inotropy Heart cardiac Cardiovascular Receptors h2-histamine receptor |
| Citations | 16 |
| Key finding | LSD increases cardiac force and rate through activation of 5-HT4 serotonin receptors and H2 histamine receptors. |
Abstract
Lysergic acid diethylamide (LSD) is an artificial hallucinogenic drug. Thus, we hypothesized that LSD might act 5-HT4 serotonin receptors and/or H2 histamine receptors. We studied isolated electrically stimulated left atrial preparations, spontaneously beating right atrial preparations, and spontaneously beating Langendorff-perfused hearts from transgenic mice with cardiomyocyte-specific overexpression of the human 5-HT4 receptor (5-HT4-TG) or of the H2-histamine receptor (H2-TG). For comparison, we used wild type littermate mice (WT). Finally, we measured isometric force of contraction in isolated electrically stimulated muscle strips from the human right atrium obtained from patients during bypass surgery. LSD (up to 10 µM) concentration dependently increased force of contraction and beating rate in left or right atrial preparations from 5-HT4-TG (n = 6, p < 0.05) in 5-HT4-TG atrial preparations. The inotropic and chronotropic effects of LSD were antagonized by 10 µM tropisetron in 5-HT4-TG. In contrast, LSD (10 µM) increased force of contraction and beating rate in left or right atrial preparations, from H2-TG. After pre-stimulation with cilostamide (1 µM), LSD (10 µM) increased force of contraction in human atrial preparations (n = 6, p < 0.05). The contractile effects of LSD in human atrial preparations could be antagonized by 10 µM cimetidine and 1 µM GR 125487. LSD leads to H2-histamine receptor and 5-HT4-receptor mediated cardiac effects in humans.