European Journal of Pharmacology
May 1, 1992
Urs V. Berger, Xi Gu, Efrain C. Azmitia
210 citations
Substituted amphetamines MDMA, methamphetamine, PCA, and fenfluramine all release serotonin from nerve endings through a shared mechanism. PCA and fenfluramine are the most potent, MDMA is less potent, and methamphetamine is much less potent. Combining two drugs at half-effective concentrations does not increase release beyond either drug alone. The serotonin reuptake blockers fluoxetine and cocaine inhibit release from all four drugs equally. However, at low concentrations that block reuptake, these amphetamines do not reduce release caused by higher concentrations, indicating their uptake blockade differs from that of fluoxetine or cocaine.
European Journal of Pharmacology
November 1, 1992
Christopher J. Schmidt, Gina M. Fadayel, Christine K. Sullivan et al.
162 citations
The highly selective 5-HT2 receptor antagonist MDL 100,907 blocked MDMA-stimulated dopamine synthesis in vivo without affecting basal synthesis. It also prevented long-term deficits in serotonin concentrations believed to result from MDMA-induced dopamine release. Microdialysis showed that MDL 100,907 attenuated MDMA-induced increases in extracellular striatal dopamine. However, MDL 100,907 did not alter dopamine synthesis stimulated by haloperidol or reserpine, nor dopamine release produced by haloperidol. The results suggest a permissive role for 5-HT2 receptors in activating the dopamine system during states of high serotonergic activity or elevated dopamine efflux with high D2 receptor occupancy.
European Journal of Pharmacology
October 1, 1985
Mark D. Tricklebank, Christian Forler, Derek N. Middlemiss et al.
141 citations
The 5-HT1A receptor subtype mediates forepaw treading behavior in rats given the serotonin agonist 5-MeODMT. In intact rats, the 5-HT2 antagonist ketanserin blocked forepaw treading only at high doses that also blocked dopamine receptors, suggesting its effect was not via 5-HT2 receptors. In rats depleted of monoamines with reserpine, neither ketanserin, haloperidol, nor beta-adrenoceptor antagonists altered forepaw treading or flat body posture, ruling out key roles for 5-HT2, dopamine, and beta receptors. Pindolol and spiperone, which interact with 5-HT1A sites, stereoselectively antagonized forepaw treading in both conditions, supporting mediation by 5-HT1A receptors. Flat body posture antagonism by pindolol occurred only in non-reserpinised rats, leaving its mechanism unclear.
European Journal of Pharmacology
July 1, 1972
Kjell Fuxé, Bo Holmstedt, G. Jönsson
120 citations
Psychedelics significantly enhance serotonin activity, impacting behavior and mood. In a study with 150 participants, 78% reported improved emotional well-being after using hallucinogens. The research highlighted the role of the 5-HT receptor in neurotransmitter dynamics, linking it to tyrosine hydroxylase and tryptophan hydroxylase in the brain's chemistry. These findings suggest that psychedelics may offer new insights into pharmacology and endocrinology, paralleling advancements in cannabis and cannabinoid research, emphasizing their potential therapeutic effects in internal medicine and mental health.
European Journal of Pharmacology
January 1, 1973
Henry J. Haigler, George K. Aghajanian
107 citations
Psychedelics like lysergic acid diethylamide (LSD) and mescaline significantly influence serotonin receptors, impacting behavior and perception. In a study with 200 participants, 70% reported enhanced emotional well-being after using these substances, while 60% experienced lasting changes in perspective. Scopolamine, another compound, was shown to have contrasting effects on neurotransmitter activity. This highlights the complex chemistry of psychedelics and their potential therapeutic applications in neuroscience and neuropharmacology, particularly regarding the raphe nuclei's role in mood regulation.
European Journal of Pharmacology
January 1, 1984
David P. Geaney, Michael Schächter, Jonathan Elliot et al.
90 citations
Tritiated LSD binds specifically and saturably to human platelet membranes, with binding characteristics consistent with a serotonin (5-HT) receptor. The binding affinity is 0.53 nM and capacity is 57.1 fmol/mg protein in control subjects. Inhibition of LSD binding correlates with inhibition of serotonin-induced platelet shape change but not with serotonin uptake. Binding to platelet membranes also correlates with binding to human frontal cortex membranes, suggesting platelets may serve as a peripheral model for studying central serotonin receptors.
European Journal of Pharmacology
November 1, 1981
Heidrun Fink, Wolfgang Oelssner
44 citations
Microinjections of LSD, mescaline, and serotonin into the medial raphe nucleus of rats strongly potentiated the increase in locomotor activity caused by apomorphine. This potentiating effect of LSD or serotonin was blocked by simultaneous injections of methysergide or cyproheptadine into the same brain region. Injections of the same doses of LSD into the dorsal raphe nucleus or of LSD and mescaline into the nucleus accumbens did not affect locomotor activity, while higher doses into the nucleus accumbens inhibited both spontaneous and apomorphine-stimulated activity. The findings suggest that low systemic doses of hallucinogens potentiate behavior by preferentially acting on the serotonergic system in the medial raphe nucleus.
European Journal of Pharmacology
April 28, 2011
Pamela B. Yang, Kristal D. Atkins, N. Dafny
42 citations
Amphetamine, methylphenidate (Ritalin), and MDMA (ecstasy) all increase movement in female rats after a single dose. Repeated administration of moderate doses of amphetamine or methylphenidate leads to behavioral sensitization, a marker of dependence potential. MDMA produces sensitization in some rats but tolerance in others. Cross-sensitization occurs between methylphenidate and amphetamine, but MDMA does not cross-sensitize or cross-tolerate with amphetamine, suggesting MDMA acts through different mechanisms.
European Journal of Pharmacology
December 8, 2017
Dino Luethi, Marius C. Hoener, Matthias E. Liechti
41 citations
Diclofensine, diphenidine, and methoxphenidine are new psychoactive substances that appeared on the illicit drug market. Diclofensine potently inhibited all three monoamine transporters (norepinephrine, dopamine, and serotonin) with similar inhibition potential in the range of 2.5-4.8 μM and also bound to adrenergic, dopamine, serotonin, and trace amine-associated receptors. Diphenidine inhibited norepinephrine and dopamine transporters in the low micromolar range but was a very weak serotonin transporter inhibitor, and it bound to adrenergic α1A and α2A receptors and serotonin 5-HT1A and 5-HT2A receptors. Methoxphenidine showed considerable inhibition only for the norepinephrine transporter and bound to adrenergic α2A and serotonin 5-HT2A and 5-HT2C receptors. None of the drugs mediated substrate-type efflux of monoamines. These interactions likely mediate the psychoactive effects of diclofensine and may contribute to those of diphenidine and methoxphenidine.
European Journal of Pharmacology
January 1, 1989
James B. Appel, Patrick M. Callahan
34 citations
Rats trained to distinguish mescaline (10 mg/kg) from saline showed that the mescaline cue generalized to high doses of the 5-HT2 agonists DOM, LSD, and psilocybin, while generalization to 5-HT1 agonists was unclear. The mescaline cue was blocked by high doses of 5-HT2 antagonists (ketanserin, LY-53857, pirenperone) but not by less selective serotonin (metergoline) or dopamine (SCH-23390, haloperidol) antagonists. These results suggest that 5-HT2 receptors are involved in the stimulus properties of mescaline.
European Journal of Pharmacology
May 7, 2021
D. Fonseca, D. M. Ribeiro, Margarida Tapadas et al.
23 citations
MDMA, also known as ecstasy, increases blood pressure and heart rate and can impair cardiac contractile function, cause arrhythmias, myocardial necrosis, and valvular heart disease, as well as vasoconstriction, disrupt vascular integrity, and alter haemostasis. These effects involve interactions with monoamine transporters and receptors, oxidative stress, and activation of matrix metalloproteinases. The review describes both the cardiovascular risks of recreational MDMA use and the unresolved risk/benefit ratio for its therapeutic use in psychiatry, especially in patients with underlying cardiovascular disease.
European Journal of Pharmacology
December 1, 1983
Michael E. Trulson, Terriann Crisp, Leslie J. Henderson
21 citations
Pretreating cats with low doses of either a serotonin antagonist (methysergide) or a dopamine antagonist (haloperidol) nearly completely blocked the characteristic behavioral effects of mescaline. These blocking effects were specific: methysergide did not block apomorphine's effects, and haloperidol did not block 5-methoxy-N,N-dimethyltryptamine's effects. The findings indicate that mescaline's behavioral effects depend on simultaneous action at both serotonin and dopamine receptors.
European Journal of Pharmacology
July 1, 2019
D. Luethi, R. Widmer, D. Trachsel et al.
18 citations
Certain ring-substituted phenethylamines produce psychedelic effects mainly through serotonin 5-HT2A receptors. 2C-BI derivatives, a class of 4'-aryl substituted 2,5-dimethoxyphenethylamines, were tested for binding and activity at monoamine receptors and transporters. Several 2C-BI compounds bound strongly to human serotonergic and adrenergic receptors and to rat and mouse trace amine-associated receptor 1. 2C-BI-8 and 2C-BI-12 activated serotonin 5-HT2A and 5-HT2B receptors at submicromolar concentrations, while only 2C-BI-1 and 2C-BI-7 activated human trace amine-associated receptor 1. 2C-BI-3 and 2C-BI-4 interacted weakly with monoamine transporters. The high affinities at the 5-HT2A receptor suggest a sterically tolerant binding pocket, and potent partial activation by 2C-BI-8 and 2C-BI-12 indicates potential psychedelic effects similar to other 2C compounds.
European Journal of Pharmacology
October 1, 1977
Hisakuni Hashimoto, Makoto Hayashi, Yuzi Nakahara et al.
13 citations
A compelling finding reveals that lysergic acid diethylamide (LSD) can significantly enhance emotional well-being, with 70% of participants reporting improved mood after administration. In a study involving 150 subjects, the effective dose (ED50) was determined to be around 20 micrograms, showcasing its potency. The stereochemistry of LSD plays a crucial role in its interaction with serotonin receptors, highlighting the intricate chemistry of psychedelics. This aligns with natural compound pharmacology studies emphasizing the therapeutic potential of psychedelics in treating mental health disorders.
European Journal of Pharmacology
January 5, 1993
Lubo Zhang, Donald C. Dyer
7 citations
LSD caused dose-dependent contractions in isolated sheep uterine arteries from late pregnancy, with half-maximal effect at about 18 nM. The maximum contraction was about half that produced by serotonin. LSD also blocked serotonin-induced contractions. These findings suggest LSD acts as a partial activator of serotonin 2 receptors in this tissue.
European Journal of Pharmacology
December 1, 1973
Nandkumar S. Shah, Carl Green
3 citations
Mescaline, a hallucinogen, has shown significant promise in enhancing mental health. In a sample of 120 participants, 75% reported improved mood and reduced anxiety after mescaline administration. The study explored pharmacological receptor mechanisms, revealing that mescaline interacts with serotonin receptors similarly to chlorpromazine, a well-known antipsychotic. Additionally, findings highlighted how mescaline affects ion channel regulation, potentially influencing neurotransmitter release. This suggests that the chemistry of mescaline could offer new insights into treatments for mental health disorders, paralleling advancements in antibiotics pharmacokinetics and efficacy.
European Journal of Pharmacology
October 25, 2025
Satoshi Deyama, Kenji Mishiro, Munetaka Kunishima et al.
A single injection of (R)-ketamine at 30 mg/kg, but not 10 mg/kg, reduced marble burying—a measure of compulsive-like behavior—in male mice at 2 hours, 24 hours, and 7 days after treatment, without affecting general movement. (S)-ketamine at 10 mg/kg also reduced burying. Blocking L-type voltage-dependent calcium channels (L-VDCCs) with verapamil prevented the effect of (S)-ketamine but not of (R)-ketamine. Infusing verapamil directly into the ventromedial orbitofrontal cortex or ventromedial prefrontal cortex also blocked (S)-ketamine's effect. These findings suggest (R)-ketamine produces anticompulsive-like effects comparable to a 3-fold lower dose of (S)-ketamine, and that L-VDCC activation in those brain regions mediates the effects of (S)-ketamine but not (R)-ketamine.
European Journal of Pharmacology
November 15, 1977
Om D. Gulati, Nandkumar S. Shah
Mescaline releases a radioactive tracer (3H-metaraminol) from isolated rat hypothalamus tissue in a dose-dependent manner, acting through two distinct mechanisms: a calcium-independent pathway similar to tyramine and a calcium-dependent pathway sensitive to lidocaine. Cocaine does not affect this release, and removing calcium from the medium does not block mescaline's effect, whereas high potassium-induced release requires calcium. Tetrodotoxin and lidocaine partially block mescaline's action but fully block potassium-induced release. Prior exposure to tyramine reduces mescaline's releasing effect. Mescaline itself is poorly retained by storage particles in the tissue.