Severe rhabdomyolysis and acute kidney injury associated with methoxphenidine

Lam, Rex Pui Kin; Yip, Wai Lam; Tsui, Matthew Sik Hon; Ng, Sau Wah; Ching, Chor Kwan; Mak, Tony Wing Lai

doi:10.3109/15563650.2016.1157724

Cited by 11 publications

(8 citation statements)

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“…Adverse effects of dissociative arylcyclohexylamine and diarylethylamine designer drugs resemble adverse effects of traditional dissociatives, including agitation, confusion, disorientation, dissociation, hallucinations, amnesia, nystagmus, slurred speech, diaphoresis, hypertension, tachycardia, renal deficiency, nausea, ataxia, and muscle rigidity (Bäckberg et al 2015a;Dunlop et al 2019;Gerace et al 2017;Helander et al 2015;Hofer et al 2012Hofer et al , 2014 Arylcyclohexylamine and diarylethylamine designer drugs Johansson et al 2017;Shields et al 2012;Thornton et al 2017;Ward et al 2011;Wood et al 2012;Zawilska 2014;Zidkova et al 2017). In severe cases, dissociative designer drugs may potentially cause neurological impairment, manifested as cerebellar toxicity (Shields et al 2012) or rhabdomyolysis (Bäckberg et al 2015a;Lam et al 2016). Severe adverse effects associated with inhalation of the designer drug methoxetamine include seizures, hyponatremia, and sinus bradycardia (Imbert et al 2014).…”

Section: Adverse Effects Of Arylcyclohexylamine and Diarylethylamine mentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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Psychoactive substances with chemical structures or pharmacological profiles that are similar to traditional drugs of abuse continue to emerge on the recreational drug market. Internet vendors may at least temporarily sell these so-called designer drugs without adhering to legal statutes or facing legal consequences. Overall, the mechanism of action and adverse effects of designer drugs are similar to traditional drugs of abuse. Stimulants, such as amphetamines and cathinones, primarily interact with monoamine transporters and mostly induce sympathomimetic adverse effects. Agonism at l-opioid receptors and c-aminobutyric acid-A (GABA A) or GABA B receptors mediates the pharmacological effects of sedatives, which may induce cardiorespiratory depression. Dissociative designer drugs primarily act as N-methyl-D-aspartate receptor antagonists and pose similar health risks as the medically approved dissociative anesthetic ketamine. The cannabinoid type 1 (CB 1) receptor is thought to drive the psychoactive effects of synthetic cannabinoids, which are associated with a less desirable effect profile and more severe adverse effects compared with cannabis. Serotonergic 5-hydroxytryptamine-2A (5-HT 2A) receptors mediate alterations of perception and cognition that are induced by serotonergic psychedelics. Because of their novelty, designer drugs may remain undetected by routine drug screening, thus hampering evaluations of adverse effects. Intoxication reports suggest that several designer drugs are used concurrently, posing a high risk for severe adverse effects and even death.

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Section: Adverse Effects Of Arylcyclohexylamine and Diarylethylamine mentioning

confidence: 99%

Designer drugs: mechanism of action and adverse effects

2020

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“…Amnesia, loss of control, palpitations, hypertension tachycardia, and convulsions were reported . Moreover, rhabdomyolysis, acute kidney injury, and ischemic cerebral disease were observed with methoxphenidine .…”

Section: Resultsmentioning

confidence: 99%

“…The clinical cases reported in the literature concerned mainly methoxphenidine and diphenidine intoxications, with fatal outcome (death) related to methoxphenidine and diphenidine abuse in six cases [13][14][15][16][17][18][19][20]. These patients were always polysubstance consumers with associated intake of multiple NPS (synthetic cathinones, synthetic cannabinoids), with the exception of three cases of methoxphenidine intoxication, with high femoral blood concentrations of the drug (case 1: 24 mg/L, case 2: 2 mg/L, case 3: 1.36 mg/L) [17].…”

Section: R E S U L T Smentioning

confidence: 99%

“…These patients were always polysubstance consumers with associated intake of multiple NPS (synthetic cathinones, synthetic cannabinoids), with the exception of three cases of methoxphenidine intoxication, with high femoral blood concentrations of the drug (case 1: 24 mg/L, case 2: 2 mg/L, case 3: 1.36 mg/L) [17]. Amnesia, loss of control, palpitations, hypertension tachycardia, and convulsions were reported [13][14][15][16][17][18][19][20]. Moreover, rhabdomyolysis, acute kidney injury, and ischemic cerebral disease were observed with methoxphenidine [16,20].…”

Section: R E S U L T Smentioning

confidence: 99%

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Ephenidine, diphenidine, and methoxphenidine complications reported to the French Addictovigilance Network

Eiden¹,

Leone-Burgos²,

Serre³

et al. 2018

Fundamemntal Clinical Pharma

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Ephenidine, diphenidine, and methoxphenidine belong to the family of diarylethylamines that are psychoactive substances derived from lefetamine (N, N-di-methyl-1,2-diphenylethylamine, also called L-SPA). These dissociative anesthetic compounds act as potent and selective N-methyl-d-aspartate receptor antagonists and were recently classified as narcotic drugs in France. The available data suggest a significant risk of psychic and somatic complications. To obtain more information, this retrospective study analyzed all spontaneous notifications of serious cases of ephenidine, diphenidine, and methoxphenidine abuse collected by the French Addictovigilance Network from 2012 to 2016 and classified them as proven, probable, and possible. For each case, age, sex, concomitantly ingested substances, pattern of abuse of psychoactive drugs, and related complications (scored using the poisoning severity score) were collected. Eighteen cases were identified (one in 2013, five in 2015, and 12 in 2016) in 16 men (median age: 31.5 years [IQR 25-75% 27-34]). Ephenidine, diphenidine, and methoxphenidine were involved in four, seven, and 11 cases, respectively. No case was considered proven, 16 cases were considered possible, and two probable due to polysubstance abuse (co-ingestion of other new psychoactive substances). The reported clinical complications were minor in five cases, moderate in six cases, and serious in four cases, and included psychiatric, neurologic, and cardiovascular problems. This analysis indicates that the number of reported cases progressively increased from 2012 to 2016 and mainly concerned methoxphenidine. The addictive potential of these substances seems highly probable; but further investigations are needed to limit their harmful effects.

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“…Sci. 2022, 23, 2083 2 of 15 some instances, such abuse has resulted in human deaths [2]. Despite this, the recently discovered dissociative anesthetic potential for the treatment of depression has brought this group of substances to the forefront of medical interest [3][4][5][6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted

Jurásek

Rimpelová

Babor

et al. 2022

IJMS

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The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.

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Severe rhabdomyolysis and acute kidney injury associated with methoxphenidine

Cited by 11 publications

References 5 publications

Designer drugs: mechanism of action and adverse effects

Designer drugs: mechanism of action and adverse effects

Ephenidine, diphenidine, and methoxphenidine complications reported to the French Addictovigilance Network

Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted

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