Naunyn-Schmiedeberg's archives of pharmacology
June 1, 1990
W Löscher, U Witte, G Fredow et al.
48 citations
Hallucinogenic drugs that activate serotonin-2 receptors can trigger malignant hyperthermia, a life-threatening syndrome involving severe muscle rigidity, rising body temperature, acidosis, and metabolic disturbances, in pigs genetically susceptible to the condition. The drugs DOI, 5-MeO-DMT, and LSD induced fatal reactions in susceptible pigs, while pigs from resistant littermates survived. Pretreatment with serotonin-2 antagonists ketanserin or ritanserin prevented death and reduced hyperthermia and metabolic changes. The fatal effect appears driven by a sharp rise in plasma potassium from damaged muscle cells. The findings suggest that these drugs pose a risk of triggering malignant hyperthermia in genetically susceptible individuals, and that serotonin-2 antagonists may counteract the syndrome's fatality.
Naunyn-Schmiedeberg's archives of pharmacology
May 1, 2024
Rika Takaba, Daisuke Ibi, Keisuke Yoshida et al.
31 citations
Serotonergic psychedelics like psilocin (the active metabolite of psilocybin), DOI, and TCB-2 produce antidepressant-like effects in mice by activating the 5-HT2A receptor. Twenty-four hours after a single injection, treated mice showed significantly less immobility in the forced swimming test and tail-suspension test—indicating reduced behavioral despair—compared to control mice. Blocking the 5-HT2A receptor with volinanserin eliminated these antidepressant-like effects. Psilocin's effect in the forced swimming test lasted at least three weeks. In the novelty-suppressed feeding test, psilocin reduced feeding latency (an anxiolytic-like effect), but volinanserin did not block this, and DOI and TCB-2 had no effect. None of the drugs altered spontaneous movement or head-twitch response. The findings suggest 5-HT2A activation mediates antidepressant but not anxiolytic effects of these psychedelics.
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.
Naunyn-Schmiedeberg's archives of pharmacology
February 20, 2025
Atefeh Motamedi-Manesh, Mahdieh Farzin Asanjan, Hamed Fallah et al.
6 citations
A systematic review of 17 rodent studies found that ketamine's effects on brain-derived neurotrophic factor (BDNF) depend on treatment duration, species, and sex. Sub-chronic and chronic ketamine treatment decreased BDNF or had no effect in rats, and decreased BDNF in mice. Acute ketamine treatment commonly increased BDNF. One study reported inconsistent BDNF changes between male and female rats. Due to high methodological variability, there is currently no standardized method for using ketamine as a rodent model of schizophrenia.
Naunyn-Schmiedeberg's archives of pharmacology
November 1, 1996
M Reyes-Parada, C Scorza, V Romero et al.
6 citations
The novel amphetamine derivative ALEPH-2, a putative anxiolytic, produced serotonergic syndrome symptoms like forepaw treading and flat body posture in rats, along with decreased motor activity. No significant effect on head shakes was observed, though variability was high. In mice, higher doses (4 mg/kg) caused significant hypothermia. The drug showed nanomolar affinity for 5-HT2A/2C receptors (Ki = 173 nM) but only micromolar or lower affinity for 5-HT1A, benzodiazepine, and GABAA receptors. These findings suggest ALEPH-2's anxiolytic-like effects involve serotonergic mechanisms, particularly 5-HT2A/2C receptor interactions.
Naunyn-Schmiedeberg's archives of pharmacology
March 14, 2025
Shyh-Yuh Wei, Chien-Chou Su, Hsuan-Yun Hu et al.
1 citation
Ketamine use is rising, but how people actually consume it and how it contributes to death is not well understood. An analysis of 414 people who tested positive for ketamine at autopsy in Denmark from 2013 to 2019 identified four main consumption patterns. The most common pattern was ketamine combined with alcohol (49.5% of cases), followed by ketamine with new psychoactive substances (39.1%) and ketamine with methamphetamine (24.4%). Drug intoxication was the leading cause of death, followed by traffic accidents. One pattern—moderate ketamine levels with frequent polydrug use—was linked to higher suicide risk, while another—very low ketamine levels but also frequent polydrug use—was linked to higher accident risk.
Naunyn-Schmiedeberg's archives of pharmacology
June 18, 2026
Nicholas V. Cozzi
Deuterium substitution at the ring methoxy positions of the psychedelic drug 2C-B slightly increased its binding affinity at human 5-HT2A receptors, likely due to kinetic isotope effects that dampen molecular vibrations and rotations. However, deuteration did not alter the drug's ability to stimulate intracellular calcium release or recruit β-arrestin 2; all compounds showed similar low nanomolar potency and efficacy in these functional assays. No appreciable metabolism by human liver microsomes was observed for any compound during the experiment.
Naunyn-Schmiedeberg's archives of pharmacology
April 28, 2026
Yunsheng Liu, Rongde Zhong, Fenyong Yao et al.
Since 1975, research on ionotropic glutamate receptors (iGluRs) in depression has grown 7.31% annually, with the United States and China leading publication output. The field has shifted from basic synaptic mechanisms to clinical applications, particularly NMDA receptors and treatment-resistant depression. Ketamine therapy exemplifies a successful translation from preclinical models to rapid-acting antidepressants. A bibliometric analysis of 6,843 publications maps this evolution, identifies key collaborative networks, and highlights knowledge gaps to guide future development of next-generation antidepressants.
Naunyn-Schmiedeberg's archives of pharmacology
April 15, 2025
Arya Afrooghe, Elham Ahmadi, Ali Lesani et al.
Psilocin, the active metabolite of psilocybin, reduced scratching in mice by interfering with the kynurenine pathway and interacting with 5-HT2A receptors. In a study with eight mice per group, psilocin at 1 mg/kg produced the strongest antipruritic and hallucinogenic effects, as measured by head-twitch response. Combining psilocin with 1-MT further enhanced itch relief. Psilocin decreased expression of TLR-4, TNF-α, and indoleamine-2,3-dioxygenase (IDO) in skin tissue. This is the first evidence that psychedelics may combat itching, suggesting a potential new use for psilocin in conditions involving pruritus.