Naunyn-Schmiedeberg's archives of pharmacology
January 1, 2024
Ulrich Gergs, Hannes Jacob, Pauline Braekow et al.
16 citations
Lysergic 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.
Naunyn-Schmiedeberg's archives of pharmacology
July 1, 2023
Joachim Neumann, Nils Schulz, Charlotte Fehse et al.
13 citations
Bufotenin, a hallucinogenic drug, can stimulate human cardiac serotonin 5-HT4 receptors, increasing the force of contraction and beating rate. In transgenic mice expressing only the human 5-HT4 receptor in heart cells, bufotenin enhanced left atrial contraction and right atrial beating rate, with effects potentiated by a monoamine oxidase inhibitor. In isolated human atrial muscle strips, bufotenin concentration-dependently increased contraction force, reversed by the 5-HT4 antagonist tropisetron. Bufotenin also increased phosphorylation of phospholamban, a protein regulating heart muscle relaxation, in transgenic mouse and human atrial tissue. These findings indicate bufotenin acts as a positive inotropic and chronotropic agent through human 5-HT4 receptors.
Research Square
Ulrich Gergs, Hannes Jacob, Pauline Braekow et al.
1 citation
LSD increases the force and rate of heart muscle contraction by activating H2-histamine receptors in humans, and also acts as a partial agonist at 5-HT4 serotonin receptors in mice. In human atrial tissue from heart surgery patients, LSD's contractile effects were blocked by cimetidine, an H2-receptor antagonist. These findings clarify the cardiac effects of LSD, which is being studied again for psychiatric uses.