Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With increasing interest in the application of dextromethorphan in pain control, it is probable that patients will receive this drug in combination with analgesics such as opioids, giving rise to the potential for previously unobserved drug interactions. The interaction between dextromethorphan, and its pharmacologically active metabolite dextrorphan, and norpethidine, a toxic metabolite of pethidine, was examined in rats. Rats were assigned to receive dextromethorphan (0, 20 or 40 mg/kg) or dextrorphan (0, 15 or 30 mg/kg) combined with norpethidine (0, 28 or 42 mg/kg). The occurrence of seizures, myoclonic jerks and shivering was recorded for 60 min after drug administration. Norpethidine produced dose-related increases in the incidence of seizures, myoclonic jerks and shivering. Dextromethorphan, but not dextrorphan, increased the incidence of these behaviours. It is recommended that extreme caution be exercised if dextromethorphan and pethidine are to be used together.
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PMID:Interaction between dextromethorphan and norpethidine in rats. 1510

In a previous study, we demonstrated that a dextromethorphan analog, dimemorfan, has neuroprotective effects. Dextromethorphan and dimemorfan are high-affinity ligands at sigma1 receptors. Dextromethorphan has moderate affinities for phencyclidine sites, while dimemorfan has very low affinities for such sites, suggesting that these sites are not essential for the anticonvulsant actions of dimemorfan. Kainate (KA) administration (10 mg kg(-1), i.p.) produced robust convulsions lasting 4-6 h in rats. Pre-treatment with dimemorfan (12 or 24 mg kg(-1)) reduced seizures in a dose-dependent manner. Dimemorfan pre-treatment also attenuated the KA-induced increases in c-fos/c-jun expression, activator protein (AP)-1 DNA-binding activity, and loss of cells in the CA1 and CA3 fields of the hippocampus. These effects of dimemorfan were comparable to those of dextromethorphan. The anticonvulsant action of dextromethorphan or dimemorfan was significantly counteracted by a selective sigma1 receptor antagonist BD 1047, suggesting that the anticonvulsant action of dextromethorphan or dimemorfan is, at least in part, related to sigma1 receptor-activated modulation of AP-1 transcription factors. We asked whether dimemorfan produces the behavioral side effects seen with dextromethorphan or dextrorphan (a phencyclidine-like metabolite of dextromethorphan). Conditioned place preference and circling behaviors were significantly increased in mice treated with phencyclidine, dextrorphan or dextromethorphan, while mice treated with dimemorfan showed no behavioral side effects. Our results suggest that dimemorfan is equipotent to dextromethorphan in preventing KA-induced seizures, while it may lack behavioral effects, such as psychotomimetic reactions.
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PMID:The dextromethorphan analog dimemorfan attenuates kainate-induced seizures via sigma1 receptor activation: comparison with the effects of dextromethorphan. 1572 99

Dextromethorphan (DXM) has unique toxicity that may be difficult to diagnose. We present a case of a young woman who presented to our emergency department (ED) initially diagnosed with recurrent seizures. Paramedics brought a 19-year-old woman to the ED. Witnesses noted "shaking," which the patient did not recall. The patient denied fever, antecedent trauma, or neurological complaint. She was recently administered lamotrigine for bipolar disorder. She was a former alcoholic with no history of developing withdrawal. She admitted to marijuana use but denied use of any other illicit substances. Her vital signs and physical examination were unremarkable. She had a normal brain computed tomography, electrocardiogram, and laboratory evaluation. There was no alcohol detected. Her urine drug screen was negative for opiates, benzodiazepines, cocaine, amphetamines, barbiturates, phencyclidine, and tricyclic antidepressants. She was diagnosed with new-onset seizure and discharged home. No abnormalities were seen in the brain magnetic resonance imaging scan and electroencephalogram. She was scheduled for a cardiac syncope workup, but never followed through. Two months later, she presented to the hospital again for a similar complaint. Coworkers reported witnessing sudden tonic-clonic movements and confusion. On ED presentation, the patient was tachycardic with a heart rate of 110 beats/min and had horizontal nystagmus. She was alert with a flat affect. She did not recall events but answered questions appropriately. Repeat radiographic and laboratory evaluations were normal including urine drug screen and computed tomography. Upon questioning, she admitted to abusing DXM for the past several months. A serum DXM level at this time was 988.3 ng/mL. She was admitted to the hospital for 24 hours without sequelae. All further diagnostic testing was cancelled, and she was referred to a drug rehabilitation program. Abuse of DXM is increasing in incidence. The serum level of our patient was almost 10-fold greater than the reported therapeutic level. The toxicity of DXM is unique, and abuse should be considered in all patients presenting to the ED with new-onset seizure. Dextromethorphan abuse should be considered in young adults who present with previously undiagnosed seizure activity.
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PMID:Dextromethorphan abuse masquerading as a recurrent seizure disorder. 2137 23

Dextromethorphan (DM) is a commonly used antitussive and is currently the only FDA-approved pharmaceutical treatment for pseudobulbar affect. Its safety profile and diverse pharmacologic actions in the central nervous system have stimulated new interest for repurposing it. Numerous preclinical investigations and many open-label or blinded clinical studies have demonstrated its beneficial effects across a variety of neurological and psychiatric disorders. However, the optimal dose and safety of chronic dosing are not fully known. This review summarizes the preclinical and clinical effects of DM and its putative mechanisms of action, focusing on depression, stroke, traumatic brain injury, seizure, pain, methotrexate neurotoxicity, Parkinson's disease and autism. Moreover, we offer suggestions for future research with DM to advance the treatment for these and other neurological and psychiatric disorders.
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PMID:Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders. 2682 4

Dextromethorphan (DM) is a dextrorotatory isomer of levorphanol, a typical morphine-like opioid. When administered at supra-antitussive doses, DM produces psychotoxic and neurotoxic effects in humans. Although DM abuse has been well-documented, few studies have examined the effects of high-dose DM. The present study aimed to explore the effects of a single high dose of DM on mortality and seizure occurrence. After intraperitoneal administration with a high dose of DM (80mg/kg), Sprague-Dawley rats showed increased seizure occurrence and intensity. Hippocampal expression levels of N-methyl-d-aspartate (NMDA) receptor subunits (GluN1<GluN2A<GluN2B), c-Fos and pro-apoptotic factors (Bax and cleaved caspase-3) were upregulated by DM treatment; while levels of anti-apoptotic factors (Bcl-2 and Bcl-xL) were downregulated. Consistently, DM also induced ultrastructural degeneration in the hippocampus. A non-competitive NMDA receptor antagonist, MK-801, attenuated these effects of high-dose DM, whereas an opioid antagonist, naloxone, did not affect DM-induced neurotoxicity. Moreover, pretreatment with a highly specific GluN2B subunit inhibitor, traxoprodil, was selectively effective in preventing DM-induced c-Fos expression and apoptotic changes. These results suggest that high-dose DM produces convulsive behaviors by activating GluN2B/NMDA signaling that leads to pro-apoptotic changes.
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PMID:MK-801, but not naloxone, attenuates high-dose dextromethorphan-induced convulsive behavior: Possible involvement of the GluN2B receptor. 2891 51


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