European journal of pharmacology
July 7, 1988
P C Moser, P H Redfern
21 citations
Four benzodiazepines (diazepam, clonazepam, oxazepam, and clobazam) potentiated head-twitch responses in mice induced by directly acting serotonin receptor agonists (5-MeODMT, quipazine, mescaline) but not by the indirectly acting agonist 5-HTP, which was sometimes inhibited. The potentiation of 5-MeODMT by clonazepam (10 mg/kg) was not blocked by flumazenil, bicuculline, or serotonin depletion, nor mimicked by muscimol (which inhibited head-twitches). These findings suggest the potentiation occurs postsynaptically and is not mediated by benzodiazepine receptors. Failure to potentiate 5-HTP responses likely results from reduced serotonin neuronal activity via benzodiazepine receptors, since co-administration of flumazenil and clonazepam potentiated 5-HTP effects while each alone had no effect.
European journal of pharmacology
July 30, 1982
J Heym, G F Steinfels, B L Jacobs
21 citations
In freely moving cats, neurons in the dorsal raphe nucleus (DRN) are much more sensitive to the psychedelic compounds 5-MeO-DMT and LSD than neurons in the nucleus raphe pallidus (NRP). Low, behaviorally effective doses of these drugs strongly suppress activity in DRN neurons, while NRP neurons remain largely unaffected. This differential sensitivity suggests a unique autoregulatory control mechanism within distinct brain regions, where serotonin-producing neurons respond differently depending on their neuroanatomical location.
European journal of pharmacology
December 17, 1981
R A Glennon, J A Rosecrans, R Young
21 citations
Rats learned to distinguish an injection of the hallucinogen 5-methoxy-N,N-dimethyltryptamine (5-OMe DMT) from saline in a two-lever drug discrimination task. Once they reliably identified the drug, 36 different phenylisopropylamine compounds were tested to see if they produced similar effects. The compounds fell into three groups: those that fully mimicked 5-OMe DMT, those that partially did, and those that did not. The findings suggest that certain phenylisopropylamines, unlike amphetamine, can produce hallucinogen-like effects in rats, likely involving serotonin pathways.
European journal of pharmacology
October 8, 1997
I M Maisonneuve, K E Visker, G L Mann et al.
20 citations
Ibogaine and two related compounds (noribogaine and 18-methoxycoronaridine) both inhibit and later enhance cocaine-induced hyperactivity in rats, depending on timing. When given 1 hour before cocaine, all three agents reduced the hyperactivity caused by cocaine. When given 19 hours before cocaine, they instead amplified it. These opposite, time-dependent effects explain conflicting findings in earlier research and were not caused by the drugs' own effects on movement.
European journal of pharmacology
December 19, 1996
A S Schneider, J E Nagel, S J Mah
20 citations
Low concentrations of ibogaine (1-10 microM) selectively inhibit nicotinic receptor-mediated catecholamine release in cultured chromaffin cells, while higher concentrations (100 microM) block additional modes of release. This suggests ibogaine acts at the nicotinic acetylcholine receptor, possibly at the ion channel site, clarifying one mechanism underlying its putative anti-addictive properties.
European journal of pharmacology
November 25, 1983
R A Shephard, P L Broadhurst
20 citations
In rats selectively bred for avoidance learning, the drug 5-MeODMT (2.5 mg/kg) reduced feeding in a novel environment, while diazepam (1 mg/kg), methysergide, and 1-propranolol (6 mg/kg) increased it; d-propranolol had no effect. Roman Low Avoidance rats were most sensitive to all drugs and showed the strongest neophobia. Female Roman High and Control Avoidance rats were more sensitive to 5-MeODMT than males. These strain and sex differences suggest links between arousal, biochemical traits, and drug responsiveness.
European journal of pharmacology
June 3, 1983
O G Berge, D Chacho, K Hole
20 citations
5-MeO-DMT, a psychedelic compound, inhibits the reuptake of serotonin in rat brain tissue at concentrations between 0.5 and 500 micromolar, affecting the striatum, hippocampus, and hypothalamus. At higher concentrations (10 micromolar), it also inhibits dopamine reuptake and triggers the release of both serotonin and dopamine from nerve endings. These findings suggest that 5-MeO-DMT's effects as a serotonin agonist may involve blocking reuptake, not just directly stimulating receptors as previously thought.
European journal of pharmacology
June 16, 2000
K K Szumlinski, I M Maisonneuve, S D Glick
19 citations
Ibogaine, given to rats 19 hours before a cocaine challenge, reversed a key brain change caused by repeated cocaine use: the sensitized dopamine response in the nucleus accumbens. While ibogaine did not alter the dopamine increase from a single cocaine dose, it eliminated the amplified dopamine release that normally occurs in cocaine-sensitized animals. This effect on neuroadaptation may underlie ibogaine's proposed anti-addictive properties.
European journal of pharmacology
January 15, 1985
M E Trulson, G F Keltch
18 citations
Repeated doses of the psychedelic compound 5-MeODMT in rats rapidly produced tolerance to its behavioral effects, with the effective dose doubling and the duration of the syndrome dropping from about 15 minutes to just over 1 minute. This tolerance completely vanished within 4 hours after stopping treatment. The effect was not caused by changes in how much drug entered the brain, but appeared to result from reduced binding of the drug to serotonin receptors. These findings contradict earlier reports that claimed no tolerance develops to 5-MeODMT.
European journal of pharmacology
December 5, 1996
R A Rabin, J C Winter
17 citations
Ibogaine and its metabolite noribogaine do not directly alter adenylyl cyclase activity in the rat brain, but they enhance the inhibition of this enzyme caused by morphine and serotonin. In the frontal cortex, midbrain, and striatum, both compounds amplified morphine's effect; in the hippocampus, they boosted serotonin's effect. Ibogaine was more potent than noribogaine, but both were equally effective. The compounds did not affect inhibition by the muscarinic agonist carbachol. This selective potentiation of receptor-mediated inhibition may contribute to ibogaine's pharmacological actions.
European journal of pharmacology
July 9, 1987
T Nabeshima, K Ishikawa, K Yamaguchi et al.
17 citations
Ritanserin, a drug that blocks serotonin 5-HT2 receptors, reduced head-twitch behavior in mice caused by phencyclidine (PCP) and another serotonin-like drug, but increased head-weaving behavior. The two behaviors were inversely related. Depleting serotonin with PCPA reduced head-weaving caused by PCP plus ritanserin but not head-weaving caused by the serotonin-like drug. These results suggest PCP causes head-weaving by indirectly activating a different serotonin receptor (possibly 5-HT1) after releasing serotonin, and head-twitch by directly activating 5-HT2 receptors.
European journal of pharmacology
August 15, 2025
Niharika Singh, Puja Panwar Hazari, Parul Mittal et al.
16 citations
Depression impairs cognition, learning, and memory by disrupting brain chemistry. The monoamine hypothesis links depression to low serotonin, dopamine, and norepinephrine. Antidepressants such as SSRIs and SNRIs, which block serotonin and norepinephrine transporters, are primary treatments for major depressive disorder. Recently, psychedelics have gained importance as antidepressants. This review covers SSRIs, SNRIs, and psychedelics, their target receptors, and recent treatment advances. It also discusses the polypharmacology of psychedelics and fMRI studies that illuminate brain dynamics under psychedelics.
European journal of pharmacology
March 15, 2025
James J Gattuso, Carey Wilson, Shanshan Li et al.
16 citations
Psilocybin, a serotonergic psychedelic, shows therapeutic potential for depression and anxiety disorders. In a study using serotonin transporter knockout mice—a model for anxiety and depression—a single dose of psilocybin (1 mg/kg) failed to produce head-twitch or hyperlocomotor responses in knockout animals, unlike wild-type mice. Psilocybin did not alter anxiety- or depressive-like behaviors in either genotype, though a trend toward reduced immobility in the Porsolt swim test appeared in female wild-type mice. Female knockout mice uniquely showed anhedonia-like behavior. The findings indicate that functional serotonin transporters are necessary for psilocybin's acute behavioral effects, with implications for pharmacogenetics in humans.
European journal of pharmacology
November 9, 1993
A A Alhaider, M Hamon, G L Wilcox
15 citations
Intrathecal injection of 5-MeO-DMT, a serotonin receptor agonist, produces antinociceptive (pain-blocking) effects in mice across three behavioral tests: tail-flick, substance P, and NMDA assays. It prolonged tail-flick latency at doses of 4.6-92 nmol per mouse, an effect blocked by 5-HT3 and GABAA receptor antagonists but not by several other serotonin receptor blockers. 5-MeO-DMT inhibited biting behavior and increased scratching induced by substance P; the inhibition of biting was antagonized by 5-HT1B and GABAA antagonists, while enhanced scratching involved multiple serotonin and GABAA receptors. NMDA-induced biting was also inhibited by 5-MeO-DMT, blocked by 5-HT1B, 5-HT3, and GABAA antagonists. These findings suggest 5-MeO-DMT may promote serotonin release.
European journal of pharmacology
December 15, 2024
Ming-Ming Zhao, Ting-Ting Zhu, Dan Xu et al.
14 citations
Arketamine, the (R)-enantiomer of ketamine, reduces damage to the myelin sheath and promotes its repair in the brains of mice treated with cuprizone, a chemical that induces demyelination. The beneficial effects occur through a mechanism dependent on transforming growth factor β1 (TGF-β1). Blocking the TGF-β1 receptor with RepSox prevented arketamine's protective effects. Directly administering TGF-β1 intranasally also reduced demyelination and enhanced remyelination in the corpus callosum. These findings suggest that arketamine's effects on myelin repair rely on TGF-β1 signaling, pointing to potential therapeutic targets for demyelinating diseases like multiple sclerosis.
European journal of pharmacology
February 10, 2010
Roman Paškulin, Polona Jamnik, Natasa Obermajer et al.
13 citations
Ibogaine, known for its anti-addictive effects, alters energy metabolism in a way that is not species- or tissue-specific. In yeast (Saccharomyces cerevisiae) grown with 1 mg/l ibogaine for 5 hours, enzymes involved in energy production—glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, enolase, and alcohol dehydrogenase—were induced. This induction compensates for a drop in ATP levels observed after ibogaine exposure. The effect occurs without involvement of receptors, which are absent in yeast, indicating a direct metabolic influence rather than receptor-mediated action.
European journal of pharmacology
May 21, 2007
Beatriz Goñi-allo, Elena Puerta, Isabel Hervias et al.
13 citations
Amiloride, a drug that blocks sodium/calcium and sodium/hydrogen exchange, worsens long-term serotonin loss caused by MDMA in rats. Unlike with methamphetamine, amiloride also increases MDMA-induced hyperthermia. The antidepressant fluoxetine fully protects against serotonin depletion without affecting hyperthermia, while calcium channel blockers do not. The effect appears mediated by sodium/hydrogen exchange blockade, as dimethylamiloride produces similar results. When rats are kept at 15°C, hyperthermia does not develop and serotonin levels remain normal after seven days. These findings suggest that amiloride's enhancement of serotonin loss depends on its ability to amplify MDMA-induced hyperthermia, and that blocking sodium/hydrogen exchange may combine with hyperthermia to make serotonin nerve endings more vulnerable.
European journal of pharmacology
March 5, 2024
Hugo R Arias, Deborah Rudin, Dustin J Hines et al.
12 citations
A non-hallucinogenic compound derived from ibogamine, DM506, produces anxiolytic- and sedative-like effects in mice without causing hallucinogenic head-twitch responses. At 15 mg/kg, DM506 induces both acute and long-lasting anxiety-reducing behavior in naive and stressed mice. Repeated 5 mg/kg doses show no cumulative effects or side effects. Higher doses (40 mg/kg) cause sedation that is blocked by the 5-HT2A receptor antagonist volinanserin. DM506 binds to human 5-HT2A (Ki = 24 nM) and 5-HT2B (Ki = 16 nM) receptors, activating them with EC50 values of 9 nM and 3 nM, respectively, acting as a partial agonist compared to the full agonist DOI. Electroencephalography shows increased transition from alert to deep-sleep brain wave activity.
European journal of pharmacology
November 15, 2024
Hui Li, Wen Hu, Zhen Wu et al.
11 citations
Esketamine improves cognitive impairments and alleviates neuronal damage in mice with sepsis-associated encephalopathy by inhibiting microglia-mediated neuroinflammation. The beneficial effects of Esketamine on microglia and cognitive behavior were counteracted by the BDNF receptor antagonist K252a in both in vivo and in vitro experiments. These results suggest that Esketamine inhibits microglia-mediated neuroinflammation by activating the BDNF pathway, thereby mitigating neuronal damage and cognitive dysfunction associated with sepsis-associated encephalopathy.
European journal of pharmacology
September 15, 2023
Barbara G Ferri, Cintia O De Novais, Raquel S Bonani et al.
11 citations
Synthetic psychedelics 25H-NBOMe and 25H-NBOH, which act on serotonin 5-HT2A receptors, reduced depressive-like behavior in male adult rats. In the forced swimming test, both substances produced significantly greater motivation to escape compared to controls, suggesting antidepressant properties. All doses (0.1, 1, and 3 mg/kg) caused hallucinogenic effects as measured by head twitch responses. Locomotor activity in the open field test was unaffected except at the highest dose (3 mg/kg), which reduced movement. These findings indicate that a single dose of these compounds may have antidepressant potential, contributing to psychedelic research for psychiatric treatments.
European journal of pharmacology
October 15, 1979
M Simonovic, H Y Meltzer
11 citations
Repeated injections of the serotonin agonist 5MeODMT in rats gradually increased the prolactin-releasing effect of that drug and two other serotonin agonists, but did not change the prolactin response to anti-dopaminergic drugs. The enhanced response appears to result from sensitization of the serotonin system involved in prolactin regulation.
European journal of pharmacology
May 20, 1988
H Dabiré, C Cherqui, B Fournier et al.
10 citations
In pithed rats, serotonin (5-HT) raised blood pressure, an effect blocked by LY 53857, a selective 5-HT2 receptor antagonist, but not by antagonists of 5-HT1-like, 5-HT3, alpha-2, or alpha-1 receptors. 5-MeODMT also increased blood pressure, though less potently than 5-HT, and this effect was similarly blocked by LY 53857. Other serotonin receptor agonists—8-OH-DPAT, RU 24969, and TFMPP—were far less effective at raising blood pressure, while 5-CT lowered blood pressure. These results suggest that vasoconstriction from 5-HT and 5-MeODMT in pithed rats is primarily mediated by postjunctional 5-HT2 receptors, with postjunctional 5-HT1-like receptors playing little or no role.
European journal of pharmacology
March 15, 2025
Mingming Zhao, Akifumi Eguchi, Rumi Murayama et al.
6 citations
Intermittent MDMA administration (10 mg/kg, three times weekly for 6 weeks) reduced demyelination in the corpus callosum of mice treated with cuprizone, a chemical that induces myelin loss. The effect appears linked to changes in gut bacteria and metabolites, including β-D-allose, L-sorbose, and carnitine, which correlated negatively with specific microbes such as Romboutsia. These findings suggest MDMA may influence brain demyelination through the gut-brain axis, though further research is needed to clarify the roles of gut microbiota and metabolites.
European journal of pharmacology
March 19, 1998
S Helsley, R A Rabin, J C Winter
6 citations
Rats trained to recognize ibogaine's effects were tested with several beta-carbolines to see which ones produced similar internal sensations. 6-Methoxyharmalan fully mimicked ibogaine in 86.3% of trials, while harmaline had done so in 83.5% in earlier work. Harmine, harmane, harmalol, and tetrahydro-beta-carboline produced partial substitution, but norharmane and DMCM did not. These results suggest that some beta-carbolines share ibogaine-like effects, though whether this extends to anti-addictive properties remains unknown.
European journal of pharmacology
April 15, 2023
Amal Aburahma, Srishti Rana, Ray Larsen et al.
5 citations
MDMA (Ecstasy, Molly, or X) can cause life-threatening hyperthermia. In rats, removing the adrenal glands reduced the temperature increase after MDMA, and giving norepinephrine or corticosterone partially restored it. MDMA also changed the gut microbiome, altering the balance of bacterial groups like Firmicutes, Bacteroidetes, Actinobacteria, Verrucomicrobia, and Proteobacteria. These results indicate a link between the adrenal system, gut bacteria, and MDMA-induced hyperthermia.