Potentiation of 5-methoxy-N,N-dimethyltryptamine-induced hyperthermia by harmaline and the involvement of activation of 5-HT1A and 5-HT2A receptors.
Xi-Ling Jiang, Hong-Wu Shen, Ai-Ming Yu
Neuropharmacology February 1, 2015 DOI: 10.1016/j.neuropharm.2014.10.013 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Wild-type and CYP2D6-humanized (Tg-CYP2D6) mice |
| Interventions | Harmaline 5-MeO-DMT WAY-100635 MDL-100907 ketanserin |
| Dose | Harmaline 5 and 15 mg/kg; 5-MeO-DMT 10 and 20 mg/kg; co-administration harmaline 2, 5, or 15 mg/kg with 5-MeO-DMT 2 or 10 mg/kg |
| Topics | 5-MeO-DMT DMT Serotonin |
| Keywords | Thermoregulation Temperature control Thermal regulation Drug interaction Substance interaction Co-administration Drug synergy Polypharmacy Hyperthermia Overheating Elevated body temperature Heatstroke Neurobiology Brain receptors Serotonin receptors Neuropharmacology Receptor activation |
| Citations | 26 |
| Key findings | Co-administration of harmaline potentiates 5-MeO-DMT-induced hyperthermia through activation of both 5-HT1A and 5-HT2A receptors. |
Abstract
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and harmaline are serotonin (5-HT) analogs often abused together, which alters thermoregulation that may indicate the severity of serotonin toxicity. Our recent studies have revealed that co-administration of monoamine oxidase inhibitor harmaline leads to greater and prolonged exposure to 5-HT agonist 5-MeO-DMT that might be influenced by cytochrome P450 2D6 (CYP2D6) status. This study was to define the effects of harmaline and 5-MeO-DMT on thermoregulation in wild-type and CYP2D6-humanized (Tg-CYP2D6) mice, as well as the involvement of 5-HT receptors. Animal core body temperatures were monitored noninvasively in the home cages after implantation of telemetry transmitters and administration of drugs. Harmaline (5 and 15 mg/kg, i.p.) alone was shown to induce hypothermia that was significantly affected by CYP2D6 status. In contrast, higher doses of 5-MeO-DMT (10 and 20 mg/kg) alone caused hyperthermia. Co-administration of harmaline (2, 5 or 15 mg/kg) remarkably potentiated the hyperthermia elicited by 5-MeO-DMT (2 or 10 mg/kg), which might be influenced by CYP2D6 status at certain dose combination. Interestingly, harmaline-induced hypothermia was only attenuated by 5-HT1A receptor antagonist WAY-100635, whereas 5-MeO-DMT- and harmaline-5-MeO-DMT-induced hyperthermia could be suppressed by either WAY-100635 or 5-HT2A receptor antagonists (MDL-100907 and ketanserin). Moreover, stress-induced hyperthermia under home cage conditions was not affected by WAY-100635 but surprisingly attenuated by MDL-100907 and ketanserin. Our results indicate that co-administration of monoamine oxidase inhibitor largely potentiates 5-MeO-DMT-induced hyperthermia that involves the activation of both 5-HT1A and 5-HT2A receptors. These findings shall provide insights into development of anxiolytic drugs and new strategies to relieve the lethal hyperthermia in serotonin toxicity.
Comparable studies
Other preclinical and animal studies on 5-MeO-DMT, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells. Human primary monocyte-derived dendritic cells | 2014 | In vitro study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| Hallucinogen-like actions of 5-methoxy-N,N-diisopropyltryptamine in mice and rats. Mice and rats | 2006 | Preclinical study | |
| Agonist Properties of N,N-Dimethyltryptamine at Serotonin 5-HT2A and 5-HT2C Receptors Rats and transfected fibroblasts | 1998 | Experimental study | |
| Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat Intact rats and rats depleted of monoamines with reserpine | 1985 | Experimental study |
Citations in the library
Cited by 16
- Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response Biomedicine & Pharmacotherapy August 29, 2022
- The clinical pharmacology and potential therapeutic applications of 5‐methoxy‐N,N‐dimethyltryptamine (5‐MeO‐DMT) Journal of Neurochemistry February 12, 2022
- A narrative synthesis of research with 5-MeO-DMT. Journal of Psychopharmacology March 1, 2022
- Behavioral Changes Over Time Following Ayahuasca Exposure in Zebrafish Frontiers in Behavioral Neuroscience July 28, 2017
- Molecular Pathways of the Therapeutic Effects of Ayahuasca, a Botanical Psychedelic and Potential Rapid-Acting Antidepressant Biomolecules November 2, 2022
and 11 more in the library
Cites 23
- Clinical investigations of the therapeutic potential of ayahuasca: rationale and regulatory challenges. Pharmacology & Therapeutics May 1, 2004
- Clinical toxicology of newer recreational drugs Clinical Toxicology October 1, 2011
- Differential contributions of serotonin receptors to the behavioral effects of indoleamine hallucinogens in mice Journal of Psychopharmacology December 8, 2010
- Psychedelic 5-methoxy-N,N-dimethyltryptamine: metabolism, pharmacokinetics, drug interactions, and pharmacological actions. Current Drug Metabolism October 1, 2010
- A fatal intoxication following the ingestion of 5-methoxy-N,N-dimethyltryptamine in an ayahuasca preparation. Journal of Analytical Toxicology 2005
and 18 more in the library