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.
Naunyn-Schmiedeberg s Archives of Pharmacology
November 1, 2022
Joachim Neumann, Karyna Azatsian, Christian Höhm et al.
7 citations
Ephedrine, norephedrine, and MDMA, but not mescaline, increased the force of contraction and beating rate in isolated mouse and human heart tissue preparations, starting at concentrations of 1–3 µM. These effects were less potent than those of isoprenaline and were accompanied by increased phosphorylation of troponin’s inhibitory subunit. Cocaine or propranolol greatly attenuated the effects, suggesting these drugs act indirectly by releasing noradrenaline in the human atrium. Mescaline showed no inotropic effect even with phosphodiesterase inhibitors. The findings indicate that ephedrine, norephedrine, and MDMA can be classified as indirect sympathomimetics in human atrial muscle, which may contribute to cardiac arrhythmias and fatal intoxication.
Toxicology Letters
June 12, 2024
Joachim Neumann, Kiril Dimov, Karyna Azatsian et al.
5 citations
Psilocybin and psilocin, the hallucinogenic compounds in magic mushrooms, activate cardiac serotonin (5-HT4) receptors, increasing the force and rate of heart contractions. In isolated left and right atrial preparations from transgenic mice overexpressing the human 5-HT4 receptor, both drugs enhanced contraction force and beating rate, though their effects at 10 µM were weaker than those of 1 µM serotonin. No effects were seen in wild-type mice. In human atrial tissue, the positive inotropic effects required inhibition of phosphodiesterase III to become apparent. The effects were blocked by the 5-HT4 receptor antagonists tropisetron and GR125487, confirming that psilocybin and psilocin act as agonists on cardiac 5-HT4 receptors.
Scientific reports
February 25, 2025
Joachim Neumann, Tobias Dietrich, Karyna Azatsian et al.
2 citations
Hallucinogenic tryptamines DMT and 5-MeO-DMT increase the force of contraction and beating rate in heart muscle tissue from mice engineered to overexpress human 5-HT4 receptors, and also increase force of contraction in human atrial tissue from cardiac surgery patients. These effects are smaller than those of serotonin, reaching about 65% of serotonin's maximum inotropic effect at 10 µM in mouse left atria, and 40 ± 5% of serotonin's chronotropic effect in mouse right atria. The drugs are inactive in wild-type mice. The potency of 5-MeO-DMT is enhanced by a phosphodiesterase inhibitor, and it increases phosphorylation of phospholamban at serine 16. DMT and 5-MeO-DMT act as partial agonists at human 5-HT4 receptors.