European Journal of Clinical Pharmacology
September 1, 2003
Mats Bergstr�m, A. Grahn�n, B. L�ngstr�m
312 citations
Because three out of four drug candidates fail in clinical trials, and because costs and pressure to reduce animal experiments are rising, there is a need for better early human screening. Positron emission tomography (PET) allows non-invasive measurement of drug distribution and concentration in the human body when the drug is labeled with a positron-emitting radionuclide without altering its biochemical properties. Recent advances in rapid synthesis of labeled compounds enable many new drug candidates to be used as PET probes. The authors propose that early PET-microdosing studies, using very low drug doses, can help select or reject compounds based on human in vivo performance.
European Journal of Clinical Pharmacology
October 27, 2021
T. Lima, M. B. Visacri, P. M. Aguiar
38 citations
Ketamine and esketamine produce a rapid antidepressant effect, improving clinical response within 40 minutes to 1 week and remission within 80 minutes to 72 hours for ketamine, and 2 hours to 4 weeks for esketamine. Both drugs also reduce depression scale scores and suicidality. Oral ketamine shows no significant change in adverse events compared to control, while intranasal esketamine increases risks of dissociation, dizziness, hypoesthesia, and vertigo. However, most systematic reviews analyzed are of critically low methodological quality, and long-term efficacy and safety data remain lacking, highlighting the need for higher-quality evidence.
European Journal of Clinical Pharmacology
December 2, 2017
Patrick Vizeli, Henriette E. Meyer zu Schwabedissen, Matthias E. Liechti
15 citations
Genetic variants of the norepinephrine transporter gene (SLC6A2) weakly influence the acute cardiovascular response to MDMA (ecstasy). In a pooled analysis of eight double-blind, placebo-controlled studies involving 124 healthy subjects, carriers of the GG genotype of the rs1861647 SNP showed higher increases in heart rate and rate-pressure product after MDMA than those with one or no G alleles. Subjects with a C allele in the rs2242446 SNP had greater heart rate elevations compared with the TT genotype. The AA genotype of the rs36029 SNP was associated with higher increases in mean arterial pressure and rate-pressure product than carriers of the G allele. Two other SNPs (rs168924 and rs47958) did not alter MDMA responses. These genetic factors may play a minor role in adverse cardiovascular events during recreational MDMA use.
European Journal of Clinical Pharmacology
December 22, 2025
Claudia Pisanu, Shungo Imai, Masami Tsuchiya et al.
3 citations
Esketamine, used for treatment-resistant depression, shows potential adverse effects and drug-drug interaction signals when analyzed in real-world data. The findings highlight risks that clinicians should consider when prescribing esketamine, particularly regarding possible interactions with other medications. The analysis underscores the need for careful monitoring of patients receiving esketamine to manage and mitigate these risks.
European Journal of Clinical Pharmacology
July 1, 2025
Lingjing Yuan, Jianping He, Xiangyu Li
3 citations
Data mining of the FDA Adverse Event Reporting System (FAERS) from 2022 to 2024 identified 2,451 adverse event reports listing dextromethorphan/bupropion (D/B) as the primary suspect. Psychiatric disorders (22.07%) and nervous system disorders (18.77%) were most common, mostly in adults aged 18–44 years. Median time to onset of adverse events was 2 days. Nearly 20 novel adverse events not in the label were detected, including sensation of inebriation and panic attacks. Risk signals for suicide/self-injury with D/B were significantly lower than with bupropion or esketamine, but still warrant attention. The authors recommend careful monitoring of psychiatric and nervous system disorders and further pharmacoepidemiological research on dissociative disorders.
European Journal of Clinical Pharmacology
May 1, 2012
David M Wood, Susannah Davies, Malgorzata Puchnarewicz et al.
Methoxetamine, a ketamine derivative marketed as bladder-safe, can cause acute toxicity with dissociative and sympathomimetic symptoms. Three patients aged 28 to 42 presented to an emergency department after using methoxetamine, showing a dissociative or catatonic state similar to ketamine, along with tachycardia and hypertension. All were treated with low-dose benzodiazepines and discharged after symptoms resolved. Serum concentrations ranged from 0.09 to 0.2 mg/L; one patient also had detectable levels of 6-APB/5-APB. These cases demonstrate that methoxetamine use carries acute risks, and further research is needed to assess its bladder safety.