Methysergide 1mg tablets

Though microdosing psychedelics has become increasingly popular, its long-term effects on cardiac health remain unknown. Microdosing most commonly involves ingesting sub-threshold doses of lysergic acid diethylamide (LSD), psilocybin, or other psychedelic drugs 2-4 times a week for at least several weeks, but potentially months or years. Concerningly, both LSD and psilocybin share structural similarities with medications which raise the risk of cardiac fibrosis and valvulopathy when taken regularly, including methysergide, pergolide, and fenfluramine. 3,4-Methylenedioxymethamphetamine, which is also reportedly used for microdosing, is likewise associated with heart valve damage when taken chronically. In this review, we evaluate the evidence that microdosing LSD, psilocybin, and other psychedelics for several months or more could raise the risk of cardiac fibrosis. We discuss the relationship between drug-induced cardiac fibrosis and the 5-HT2B receptor, and we make recommendations for evaluating the safety of microdosing psychedelics in future studies.

Abstract licence: CC BY-NC

Brief hypoxic episodes drive neuroplasticity in animal models and humans. Pretreatment with an allosteric AMPA receptor (R) modulator ("ampakine") enables a single hypoxic exposure to induce sustained increases in phrenic motor activity ("phrenic motor facilitation" or pMF). Phrenic nerve activity was recorded in anesthetized rats to determine if the ampakine-hypoxia (A-H) combination is unique in its ability to evoke pMF and to determine its underlying mechanisms. Pairing ampakine CX717 with brief moderate or severe hypercapnia failed to produce pMF. Pairing doxapram, a respiratory stimulant, with hypoxia did not produce pMF. We then sequentially tested the hypotheses that A-H induced pMF requires spinal serotonin, adenosine or NMDA receptor activation. Cervical intrathecal delivery of serotonin (methysergide) or adenosine 2A receptor (MSX-3) antagonists prior to A-H failed to prevent pMF. In contrast, the NMDA-R blocker MK-801 prevented pMF when administered before but not after A-H. Lastly, as a step in the translational pathway, we tested the safety and efficacy of acute A-H exposure in unanesthetized rats with indwelling diaphragm electromyogram (EMG) wires after cervical spinal cord injury (SCI). A-H was well tolerated, and at 3 months post-SCI, increased diaphragm EMG output. We conclude that the mechanism driving sustained increases in phrenic motor output after A-H is independent of spinal adenosine or serotonin receptor activation, but requires spinal NMDA-R activation for the induction, but not maintenance of A-H pMF. Ampakine pretreatment may be useful to increase the efficacy of hypoxia-based rehabilitation paradigms after SCI, particularly since clinical trials report a substantial number of "low-responders".

Abstract licence: CC BY-NC-ND

Abstract Introduction and Objectives Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disorder characterized by the development of fibrotic tissue around the abdominal aorta, often leading to ureteral entrapment and renal dysfunction. Several pharmacological agents have been implicated as potential triggers. Despite scattered case reports and limited series, comprehensive quantitative assessments of drug-related RPF signals remain scarce. This study aimed to identify and quantify signals of disproportionate reporting of RPF associated with specific medications using data from a large pharmacovigilance database. Methods The FDA Adverse Event Reporting System (FAERS) was queried from 1969 to 2025 to identify RPF-related adverse event reports. Drugs associated with more than twenty RPF reports were included in a disproportionality analysis; this threshold was arbitrarily defined to focus on medications with a relatively higher volume of reports. This selection aimed to ensure adequate statistical power and reduce noise from underreported associations. For each, the Reporting Odds Ratio (ROR), 95% Confidence Intervals (CI), Proportional Reporting Ratio (PRR), chi-square values, and p-values were calculated. A signal was considered statistically significant when PRR > 2, chi-square > 4, and p Results A total of 1,013 RPF cases were identified. Of these, 392 (38.7%) were linked to twelve drugs, each associated with more than twenty RPF reports. Methysergide showed the strongest association (ROR: 5332.28; 95% CI: 4292.96–6623.21; PRR: 4604.65; chi-square: 429546.30; p Conclusions This pharmacovigilance analysis identified multiple medications, spanning different therapeutic classes, that demonstrated a disproportionate association with reports of RPF. Notably, some drugs with well-established safety profiles also emerged as potential signals, warranting increased clinical awareness. While this analysis reveals pharmacovigilance signals suggestive of drug-induced RPF, the observational nature of FAERS data limits causal inference. These findings underscore the need for further clinical research and mechanistic studies to better understand the etiopathogenic role of these agents in RPF development.

Abstract licence: CC BY

Pharmacological neuromodulation of swallowing may represent a promising therapeutic option to treat dysphagia. Previous studies suggested a serotonergic control of swallowing, but mechanisms remain poorly understood. Here, we investigated the effects of the serotonergic agonist quipazine on swallowing, using the arterially perfused working heart-brainstem (in situ) preparation in rats. Systemic injection of quipazine produced single swallows with motor patterns and swallow-breathing coordination similar to spontaneous swallows, and increased swallow rate with moderate changes in cardiorespiratory functions. Methysergide, a 5-HT2 receptor antagonist, blocked the excitatory effect of quipazine on swallowing, but had no effect on spontaneous swallow rate. Microinjections of quipazine in the nucleus of the solitary tract were without effect. In contrast, similar injections in caudal medullary raphe nuclei increased swallow rate without changes in cardiorespiratory parameters. Thus, quipazine may exert an excitatory effect on raphe neurons via stimulation of 5-HT2A receptors, leading to increased excitability of the swallowing network. In conclusion, we suggest that pharmacological stimulation of swallowing by quipazine in situ represents a valuable model for experimental studies. This work paves the way for future investigations on brainstem serotonergic modulation, and further identification of neural populations and mechanisms involved in swallowing and/or swallow-breathing interaction.

Abstract licence: CC BY

The blue-green algae Aphanizomenon flos aquae (AFA), rich in beneficial nutrients, exerts various beneficial effects, acting in different organs including the gut. Klamin® is an AFA extract particularly rich in β-PEA, a trace-amine considered a neuromodulator in the central nervous system. To date, it is not clear if β-PEA exerts a role in the enteric nervous system. The aims of the present study were to investigate the effects induced by Klamin® on the human distal colon mechanical activity, to analyze the mechanism of action, and to verify a β-PEA involvement. The organ bath technique, RT-PCR, and immunohistochemistry (IHC) were used. Klamin® reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions. EPPTB, a trace-amine receptor (TAAR1) antagonist, significantly antagonized the inhibitory effects of both Klamin® and exogenous β-PEA, suggesting a trace-amine involvement in the Klamin® effects. Accordingly, AphaMax®, an AFA extract containing lesser amount of β-PEA, failed to modify colon contractility. Moreover, the Klamin® effects were abolished by tetrodotoxin, a neural blocker, but not by L-NAME, a nitric oxide-synthase inhibitor. On the contrary methysergide, a serotonin receptor antagonist, significantly antagonized the Klamin® effects, as well as the contractility reduction induced by 5-HT. The RT-PCR analysis revealed TAAR1 gene expression in the colon and the IHC experiments showed that 5-HT-positive neurons are co-expressed with TAAR1 positive neurons. In conclusion, the results of this study suggest that Klamin® exerts spasmolytic effects in human colon contractility through β-PEA, that, by activating neural TAAR1, induce serotonin release from serotoninergic neurons of the myenteric plexus.

Abstract licence: CC BY