Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

García-Alonso, Daniela; Morgenstern-Kaplan, Dan; Cohen-Welch, Ariel; Lozano-Cuenca, Jair; López-Canales, Jorge Skiold

doi:10.3390/medsci7030039

Cited by 2 publications

(2 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Amphetamine-induced vasodilation was already described for amphetamine–based pharmaceuticals like clobenzorex 16 in isolated aortic rings. For amphetamine-based drugs like fenproporex this effect was shown to depend on an intact endothelium 17 . Summarizing, vasodilation in acute response to amphetamines shall be considered as a general mechanism of amphetamine—based compounds.…”

Section: Discussionmentioning

confidence: 99%

Amphetamine increases vascular permeability by modulating endothelial actin cytoskeleton and NO synthase via PAR-1 and VEGF-R

Böttner,

Fischer-Schaepmann,

Werner

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Abuse of amphetamine-type stimulants is linked to cardiovascular adverse effects like arrhythmias, accelerated atherosclerosis, acute coronary syndromes and sudden cardiac death. Excessive catecholamine release following amphetamine use causes vasoconstriction and vasospasms, over time leading to hypertension, endothelial dysfunction or even cardiotoxicity. However, immediate vascular pathomechanisms related to amphetamine exposure, especially endothelial function, remain incompletely understood and were analyzed in this study. Pharmaco-pathological effects of acute d-amphetamine-sulfate (DAM) were investigated ex vivo using contraction–force measurements of rat carotid artery rings and in vitro using label-free, real-time electrochemical impedance spectroscopy (EIS) on endothelial and smooth muscle cells. Specific receptor and target blocking was used to identify molecular targets and to characterize intracellular signaling. DAM induced vasodilation represented by 29.3±2.5% decrease in vascular tone (p<0.001) involving vascular endothelial growth factor receptor (VEGF-R) and protease activated receptor 1 (PAR-1). EIS revealed that DAM induces endothelial barrier disruption (−75.9±1.1% of initial cellular impedance, p<0.001) also involving VEGF-R and PAR-1. Further, in response to DAM, Rho-associated protein kinase (ROCK) mediated reversible contraction of actin cytoskeleton resulting in endothelial barrier disruption. Dephosphorylation of Serine1177 (−50.8±3.7%, p<0.001) and Threonine495 (−44.8±6.5%, p=0.0103) of the endothelial NO synthase (eNOS) were also observed. Blocking of VEGF-R and PAR-1 restored baseline eNOS Threonine495 phosphorylation. DAM induced vasodilation, enhanced vascular permeability and actin cytoskeleton contraction and induced eNOS hypophosphorylation involving VEGF-R, PAR-1 and ROCK. These results may contribute to a better understanding of severe adverse cardiovascular effects in amphetamine abuse.

show abstract

Section: Discussionmentioning

confidence: 99%

Amphetamine increases vascular permeability by modulating endothelial actin cytoskeleton and NO synthase via PAR-1 and VEGF-R

Böttner,

Fischer-Schaepmann,

Werner

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Amfepramone (2-diethylaminopropiophenon) stimulates the central nervous system to suppress appetite by increasing the release of catecholamines (dopamine and noradrenaline) in the hypothalamus and further limits their reuptake [74]. Subsequently, the drug is used as a short-term anorectic agent for the treatment of obesity [75].…”

Section: Amfepramone (Diethylpropion)mentioning

confidence: 99%

Counterfeit formulations: analytical perspective on anorectics

2021

View full text Add to dashboard Cite

Purpose This paper examines the scope of anorectics in counterfeit weight-reducing formulations and provides insight into the present state of research in determining such adulterants. Analytical techniques utilised in profiling adulterants found in slimming products, including limitations and mitigation steps of these conventional methods are also discussed. The current legal status of the anorectics and analogues routinely encountered in non-prescription slimming formulations is also explored. Methods All reviewed literature was extracted from Scopus, Web of Science, PubMed, and Google Scholar databases using relevant search terms, such as, ‘counterfeit drugs’, ‘weight loss drugs’, ‘weight-reducing drugs’, ‘slimming drugs’, ‘anorectic agents’, and ‘counterfeit anorexics’. Legislation related to anorectics was obtained from the portals of various government and international agencies. Results Anorectics frequently profiled in counterfeit slimming formulations are mostly amphetamine derivatives or its analogues. Five routinely reported pharmacological classes of adulterants, namely anxiolytics, diuretics, antidepressants, laxatives, and stimulants, are mainly utilised as coadjuvants in fake weigh-reducing formulations to increase bioavailability or to minimise anticipated side effects. Liquid and gas chromatography coupled with mass spectrometric detectors are predominantly used techniques for anorectic analysis due to the possibility of obtaining detailed information of adulterants. However, interference from the complex sample matrices of these fake products limits the accuracy of these methods and requires robust sample preparation methods for enhanced sensitivity and selectivity. The most common anorectics found in counterfeit slimming medicines are either completely banned or available by prescription only, in many countries. Conclusions Slimming formulations doped with anorectic cocktails to boost their weight-reducing efficacy are not uncommon. Liquid chromatography combined with mass spectrometry remains the gold standard for counterfeit drug analysis, and requires improved preconcentration methods for rapid and quantitative identification of specific chemical constituents. Extensive method development and validation, targeted at refining existing techniques while developing new ones, is expected to improve the analytical profiling of counterfeit anorectics significantly.

show abstract

Possible Mechanisms Involved in the Vasorelaxant Effect Produced by Anorexigenic Drugs in Rat Aortic Rings

Cited by 2 publications

References 30 publications

Amphetamine increases vascular permeability by modulating endothelial actin cytoskeleton and NO synthase via PAR-1 and VEGF-R

Amphetamine increases vascular permeability by modulating endothelial actin cytoskeleton and NO synthase via PAR-1 and VEGF-R

Counterfeit formulations: analytical perspective on anorectics

Contact Info

Product

Resources

About