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[PMID]: 28642232 [Au] Autor: Kumar M; Kumar M; Freund JM; Dillon GH [Ad] Endereço: Department of Physiology and Pharmacology, Center for Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, West Virginia (Mo.K., Mi.K., J.M.F., G.H.D.); and Center for Neuroscience Discovery, Institute for Healthy Aging, University of North Texas Health Science [Ti] Título: A Single Amino Acid Residue at Transmembrane Domain 4 of the Subunit Influences Carisoprodol Direct Gating Efficacy at GABA Receptors. [So] Source: J Pharmacol Exp Ther;362(3):395-404, 2017 Sep. [Is] ISSN: 1521-0103 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The muscle relaxant carisoprodol has recently been controlled at the federal level as a Schedule IV drug due to its high abuse potential and consequences of misuse, such as withdrawal syndrome, delusions, seizures, and even death. Recent work has shown that carisoprodol can directly gate and allosterically modulate the type A GABA (GABA ) receptor. These actions are subunit-dependent; compared with other GABA receptors, carisoprodol has nominal direct gating effects in 3 2 2 receptors. Here, using site-directed mutagenesis and whole-cell patch-clamp electrophysiology in transiently transfected human embryonic kidney 293 cells, we examined the role of GABA receptor subunit transmembrane domain 4 (TM4) amino acids in direct gating and allosteric modulatory actions of carisoprodol. Mutation of 3 valine at position 440 to leucine (present in the equivalent position in the 1 subunit) significantly increased the direct gating effects of carisoprodol without affecting its allosteric modulatory effects. The corresponding reverse mutation, 1(L415V), decreased carisoprodol direct gating potency and efficacy. Analysis of a series of amino acid mutations at the 415 position demonstrated that amino acid volume correlated positively with carisoprodol efficacy, whereas polarity inversely correlated with carisoprodol efficacy. We conclude that 1(415) of TM4 is involved in the direct gating, but not allosteric modulatory, actions of carisoprodol. In addition, the orientation of alkyl or hydroxyl groups at this position influences direct gating effects. These findings support the likelihood that the direct gating and allosteric modulatory effects of carisoprodol are mediated via distinct binding sites. [Mh] Termos MeSH primário: Aminoácidos/metabolismo Carisoprodol/farmacologia Relaxantes Musculares Centrais/farmacologia Transporte Proteico/efeitos dos fármacos Receptores de GABA-A/efeitos dos fármacos [Mh] Termos MeSH secundário: Substituição de Aminoácidos Sítios de Ligação/efeitos dos fármacos Agonistas GABAérgicos/farmacologia Células HEK293 Seres Humanos Ativação do Canal Iônico/efeitos dos fármacos Mutagênese Sítio-Dirigida Técnicas de Patch-Clamp Pentobarbital/farmacologia Receptores de GABA-A/genética Esteroides/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amino Acids); 0 (GABA Agonists); 0 (Muscle Relaxants, Central); 0 (Receptors, GABA-A); 0 (Steroids); 21925K482H (Carisoprodol); I4744080IR (Pentobarbital) [Em] Mês de entrada: 1708 [Cu] Atualização por classe: 170902 [Lr] Data última revisão: 170902 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170624 [St] Status: MEDLINE [do] DOI: 10.1124/jpet.117.242156

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[PMID]: 27798072 [Au] Autor: Lu A; Scott KS; Chan-Hosokawa A; Logan BK [Ad] Endereço: Arcadia University, Department of Chemistry, 450 S. Easton Road, Glenside, PA 19038, USA. [Ti] Título: Impact of Expanding ELISA Screening in DUID Investigations to Include Carisoprodol/Meprobamate and Zolpidem. [So] Source: J Anal Toxicol;41(2):134-139, 2017 Mar 01. [Is] ISSN: 1945-2403 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: In 2013, the National Safety Council's Alcohol Drugs and Impairment Division added zolpidem and carisoprodol and its metabolite meprobamate to the list of Tier 1 drugs that should be tested for in all suspected drug impaired driving and motor vehicle fatality investigations. We describe the validation of an enzyme linked immunosorbent assays (ELISA) for both drugs in whole blood, and the utilization of the ELISA to assess their positivity in a sample of 322 suspected impaired driving cases that was retrospectively screened using the validated assays. The occurrence of carisoprodol/meprobamate was found to be 1.2%, and for zolpidem, 1.6%. In addition, we analyzed a large dataset (n = 1,672) of Driving Under the Influence of Drugs (DUID) test results from a laboratory performing high volume DUID testing to assess the frequency of detection of both drugs after implementing the expanded NSC scope. Carisoprodol or meprobamate were found positive in 5.9% (n = 99) of these samples, while zolpidem was found positive in 5.3% (n = 89) in drivers who in many cases had been found to be negative for other drugs. Carisoprodol and zolpidem are both potent CNS depressants and are appropriate additions to the recommended NSC scope of testing. [Mh] Termos MeSH primário: Condução de Veículo Carisoprodol/sangue Depressores do Sistema Nervoso Central/sangue Dirigir sob a Influência/estatística & dados numéricos Meprobamato/sangue Piridinas/sangue Detecção do Abuso de Substâncias [Mh] Termos MeSH secundário: Dirigir sob a Influência/legislação & jurisprudência Ensaio de Imunoadsorção Enzimática Regulamentação Governamental Seres Humanos Estudos Retrospectivos Detecção do Abuso de Substâncias/legislação & jurisprudência Detecção do Abuso de Substâncias/métodos Detecção do Abuso de Substâncias/estatística & dados numéricos Estados Unidos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Central Nervous System Depressants); 0 (Pyridines); 21925K482H (Carisoprodol); 7K383OQI23 (zolpidem); 9I7LNY769Q (Meprobamate) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 170525 [Lr] Data última revisão: 170525 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161101 [St] Status: MEDLINE [do] DOI: 10.1093/jat/bkw106

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[PMID]: 27550152 [Au] Autor: Horsfall JT; Sprague JE [Ad] Endereço: Crystal Clinic Orthopaedic Center, Akron, OH, USA. [Ti] Título: The Pharmacology and Toxicology of the 'Holy Trinity'. [So] Source: Basic Clin Pharmacol Toxicol;120(2):115-119, 2017 Feb. [Is] ISSN: 1742-7843 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Combining opioids with benzodiazepines and skeletal muscle relaxants ('The Holy Trinity') has been reported to potentiate the 'high'. Through unique interactions with colocalized µ-opioid and GABA receptors, the combined use of these agents induces a synergistic increase in dopamine in the nucleus accumbens (NAc) and depression of respiration. The inhibition of GABA release mediated by µ -opioid receptor activation results in a subsequent increase in dopamine in the NAc. Benzodiazepines activate the GABA R to suppress respiration in the medullary respiratory centres. The skeletal muscle relaxant, carisoprodol, appears to bind to a unique binding domain within the GABA R to further enhance the respiratory depressant effects of the benzodiazepines. Therefore, the opioids, the benzodiazepines and carisoprodol alone or in combination are capable of inducing respiratory depression. Current guidelines for opioid prescribing recommend against the concomitant use of benzodiazepines but do not recognize the potential risk associated with the addition of skeletal muscle relaxants. [Mh] Termos MeSH primário: Analgésicos Opioides/efeitos adversos Benzodiazepinas/efeitos adversos Carisoprodol/efeitos adversos Euforia/efeitos dos fármacos Moduladores GABAérgicos/efeitos adversos Fármacos Neuromusculares/efeitos adversos Núcleo Accumbens/efeitos dos fármacos Insuficiência Respiratória/induzido quimicamente [Mh] Termos MeSH secundário: Analgésicos Opioides/administração & dosagem Animais Benzodiazepinas/administração & dosagem Carisoprodol/administração & dosagem Contraindicações Dopamina/metabolismo Cálculos da Dosagem de Medicamento Sinergismo Farmacológico Quimioterapia Combinada Moduladores GABAérgicos/administração & dosagem Seres Humanos Fármacos Neuromusculares/administração & dosagem Núcleo Accumbens/metabolismo Núcleo Accumbens/fisiopatologia Transtornos Relacionados ao Uso de Opioides/metabolismo Transtornos Relacionados ao Uso de Opioides/fisiopatologia Transtornos Relacionados ao Uso de Opioides/psicologia Guias de Prática Clínica como Assunto Respiração/efeitos dos fármacos Insuficiência Respiratória/metabolismo Insuficiência Respiratória/fisiopatologia Medição de Risco Transdução de Sinais/efeitos dos fármacos Ácido gama-Aminobutírico/metabolismo [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Analgesics, Opioid); 0 (GABA Modulators); 0 (Neuromuscular Agents); 12794-10-4 (Benzodiazepines); 21925K482H (Carisoprodol); 56-12-2 (gamma-Aminobutyric Acid); VTD58H1Z2X (Dopamine) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160824 [St] Status: MEDLINE [do] DOI: 10.1111/bcpt.12655

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[PMID]: 27398631 [Au] Autor: Acharya PC; Vasi R; Suares D [Ad] Endereço: SPP School of Pharmacy and Technology Management, SVKM's NMIMS, Mumbai 400056, India. Electronic address: pratap.aacharya@gmail.com. [Ti] Título: FTIR assay method for UV inactive drug carisoprodol and identification of degradants by RP-HPLC and ESI-MS. [So] Source: J Chromatogr B Analyt Technol Biomed Life Sci;1029-1030:16-21, 2016 Sep 01. [Is] ISSN: 1873-376X [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: A new method of analysis has been developed for UV inactive drug carisoprodol using FTIR spectroscopy. These methods were validated for various parameters according to ICH guidelines. The proposed method has also been successfully applied for the determination of the drug concentration in a tablet formulation. The method proved to be accurate (mean percentage recovery between 95 and 105%), precise and reproducible (relative standard deviation<2%), while being simple, economical and less time consuming than other methods and can be used for routine estimation of carisoprodol in the pharmaceutical industry. The developed method also implicates its utility for other UV inactive substances. The stability of the drug under various stress conditions was studied and the drug was found to be particularly susceptible to alkaline hydrolysis. Degradation products of the alkaline hydrolysis were detected by RP-HPLC and tentatively identified by ESI-MS. [Mh] Termos MeSH primário: Carisoprodol/análise Cromatografia Líquida de Alta Pressão/métodos Relaxantes Musculares Centrais/análise Espectroscopia de Infravermelho com Transformada de Fourier/métodos [Mh] Termos MeSH secundário: Cromatografia Líquida de Alta Pressão/economia Estabilidade de Medicamentos Hidrólise Fotólise Reprodutibilidade dos Testes Espectrometria de Massas por Ionização por Electrospray/economia Espectrometria de Massas por Ionização por Electrospray/métodos Espectroscopia de Infravermelho com Transformada de Fourier/economia Comprimidos Raios Ultravioleta [Pt] Tipo de publicação: JOURNAL ARTICLE; VALIDATION STUDIES [Nm] Nome de substância: 0 (Muscle Relaxants, Central); 0 (Tablets); 21925K482H (Carisoprodol) [Em] Mês de entrada: 1702 [Cu] Atualização por classe: 170823 [Lr] Data última revisão: 170823 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160712 [St] Status: MEDLINE

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[PMID]: 26872987 [Au] Autor: Kumar M; Dillon GH [Ad] Endereço: Department of Physiology and Pharmacology and Center for Neuroscience, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, WV, USA. [Ti] Título: Assessment of direct gating and allosteric modulatory effects of meprobamate in recombinant GABA(A) receptors. [So] Source: Eur J Pharmacol;775:149-58, 2016 Mar 15. [Is] ISSN: 1879-0712 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Meprobamate is a schedule IV anxiolytic and the primary metabolite of the muscle relaxant carisoprodol. Meprobamate modulates GABAA (γ-aminobutyric acid Type A) receptors, and has barbiturate-like activity. To gain insight into its actions, we have conducted a series of studies using recombinant GABAA receptors. In αxßzγ2 GABAA receptors (where x=1-6 and z=1-3), the ability to enhance GABA-mediated current was evident for all α subunit isoforms, with the largest effect observed in α5-expressing receptors. Direct gating was present with all α subunits, although attenuated in α3-expressing receptors. Allosteric and direct effects were comparable in α1ß1γ2 and α1ß2γ2 receptors, whereas allosteric effects were enhanced in α1ß2 compared to α1ß2γ2 receptors. In "extrasynaptic" (α1ß3δ and α4ß3δ) receptors, meprobamate enhanced EC20 and saturating GABA currents, and directly activated these receptors. The barbiturate antagonist bemegride attenuated direct effects of meprobamate. Whereas pentobarbital directly gated homomeric ß3 receptors, meprobamate did not, and instead blocked the spontaneously open current present in these receptors. In wild type homomeric ρ1 receptors, pentobarbital and meprobamate were ineffective in direct gating; a mutation known to confer sensitivity to pentobarbital did not confer sensitivity to meprobamate. Our results provide insight into the actions of meprobamate and parent therapeutic agents such as carisoprodol. Whereas in general actions of meprobamate were comparable to those of carisoprodol, differential effects of meprobamate at some receptor subtypes suggest potential advantages of meprobamate may be exploited. A re-assessment of previously synthesized meprobamate-related carbamate molecules for myorelaxant and other therapeutic indications is warranted. [Mh] Termos MeSH primário: Ansiolíticos/farmacologia Moduladores GABAérgicos/farmacologia Meprobamato/farmacologia Relaxantes Musculares Centrais/farmacologia Subunidades Proteicas/fisiologia Receptores de GABA-A/fisiologia [Mh] Termos MeSH secundário: Bemegrida/farmacologia Carisoprodol/farmacologia Células HEK293 Seres Humanos Ativação do Canal Iônico/efeitos dos fármacos Pentobarbital/farmacologia Subunidades Proteicas/genética Receptores de GABA-A/genética [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (Anti-Anxiety Agents); 0 (GABA Modulators); 0 (Muscle Relaxants, Central); 0 (Protein Subunits); 0 (Receptors, GABA-A); 21925K482H (Carisoprodol); 57DQA39DO2 (Bemegride); 9I7LNY769Q (Meprobamate); I4744080IR (Pentobarbital) [Em] Mês de entrada: 1612 [Cu] Atualização por classe: 170315 [Lr] Data última revisão: 170315 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160214 [St] Status: MEDLINE

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[PMID]: 26660179 [Au] Autor: Slawson MH; Johnson-Davis KL [Ad] Endereço: ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT, 84108, USA. [Ti] Título: Quantitation of Carisoprodol and Meprobamate in Urine and Plasma Using Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). [So] Source: Methods Mol Biol;1383:105-14, 2016. [Is] ISSN: 1940-6029 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Carisoprodol and meprobamate are centrally acting muscle relaxant/anxiolytic drugs that can exist in a parent-metabolite relationship (carisoprodol → meprobamate) or as a separate pharmaceutical preparation (meprobamate aka Equanil, others). The monitoring of the use of these drugs has both clinical and forensic applications in pain management applications and in overdose situations. LC-MS/MS is used to analyze urine or plasma/serum extracts with deuterated analogs of each analyte as internal standards to ensure accurate quantitation and control for any potential matrix effects. Positive ion electrospray is used to introduce the analytes into the mass spectrometer. Selected reaction monitoring of two product ions for each analyte allows for the calculation of ion ratios which ensures correct identification of each analyte, while a matrix-matched calibration curve is used for quantitation. [Mh] Termos MeSH primário: Carisoprodol/sangue Carisoprodol/urina Meprobamato/sangue Meprobamato/urina Relaxantes Musculares Centrais/sangue Relaxantes Musculares Centrais/urina Espectrometria de Massas em Tandem/métodos [Mh] Termos MeSH secundário: Cromatografia Líquida/métodos Seres Humanos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Muscle Relaxants, Central); 21925K482H (Carisoprodol); 9I7LNY769Q (Meprobamate) [Em] Mês de entrada: 1610 [Cu] Atualização por classe: 161230 [Lr] Data última revisão: 161230 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 151215 [St] Status: MEDLINE [do] DOI: 10.1007/978-1-4939-3252-8_12

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[PMID]: 25896767 [Au] Autor: Kumar M; González LA; Dillon GH [Ad] Endereço: Department of Physiology and Pharmacology and Center for Neuroscience, West Virginia University School of Medicine, Robert C. Byrd Health Sciences Center, Morgantown, WV 26506, USA. [Ti] Título: Assessment of subunit-dependent direct gating and allosteric modulatory effects of carisoprodol at GABA(A) receptors. [So] Source: Neuropharmacology;97:414-25, 2015 Oct. [Is] ISSN: 1873-7064 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Carisoprodol is a widely prescribed muscle relaxant, abuse of which has grown considerably in recent years. It directly activates and allosterically modulates α1ß2γ2 GABAARs, although the site(s) of action are unknown. To gain insight into the actions of carisoprodol, subunit-dependent effects of this drug were assessed. Whole-cell patch clamp recordings were obtained from HEK293 cells expressing α1ß2, α1ß3 or αxßzγ2 (where x = 1-6 and z = 1-3) GABAARs, and in receptors incorporating the δ subunit (modeling extrasynaptic receptors). The ability to directly gate and allosterically potentiate GABA-gated currents was observed for all configurations. Presence or absence of the γ2 subunit did not affect the ability of carisoprodol to directly gate or allosterically modulate the receptor. Presence of the ß1 subunit conferred highest efficacy for direct activation relative to maximum GABA currents, while presence of the ß2 subunit conferred highest efficacy for allosteric modulation of the GABA response. With regard to α subunits, carisoprodol was most efficacious at enhancing the actions of GABA in receptors incorporating the α1 subunit. The ability to directly gate the receptor was generally comparable regardless of the α subunit isoform, although receptors incorporating the α3 subunit showed significantly reduced direct gating efficacy and affinity. In extrasynaptic (α1ß3δ and α4ß3δ) receptors, carisoprodol had greater efficacy than GABA as a direct gating agonist. In addition, carisoprodol allosterically potentiated both EC20 and saturating GABA concentrations in these receptors. In assessing voltage-dependence, we found direct gating and inhibitory effects were insensitive to membrane voltage, whereas allosteric modulatory effects were affected by membrane voltage. Our findings demonstrate direct and allosteric effects of carisoprodol at synaptic and extrasynpatic GABAARs and that subunit isoform influences these effects. [Mh] Termos MeSH primário: Carisoprodol/farmacologia GABAérgicos/farmacologia Relaxantes Musculares Centrais/farmacologia Receptores de GABA-A/metabolismo [Mh] Termos MeSH secundário: Relação Dose-Resposta a Droga Células HEK293 Seres Humanos Potenciais da Membrana/efeitos dos fármacos Potenciais da Membrana/fisiologia Técnicas de Patch-Clamp Receptores de GABA-A/genética Transtornos Relacionados ao Uso de Substâncias/metabolismo Transfecção Ácido gama-Aminobutírico/metabolismo [Pt] Tipo de publicação: COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL [Nm] Nome de substância: 0 (GABA Agents); 0 (Muscle Relaxants, Central); 0 (Receptors, GABA-A); 21925K482H (Carisoprodol); 56-12-2 (gamma-Aminobutyric Acid) [Em] Mês de entrada: 1605 [Cu] Atualização por classe: 170220 [Lr] Data última revisão: 170220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150422 [St] Status: MEDLINE

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[PMID]: 25874243 [Au] Autor: Kurita Varoli F; Sucena Pita M; Sato S; Issa JP; do Nascimento C; Pedrazzi V [Ad] Endereço: Department of Dental Materials and Prosthodontics, Faculty of Dentistry of Ribeirão Preto, University of São Paulo, Avenida do Café s/no, Monte Alegre, 14040-904 Ribeirão Preto, SP, Brazil. [Ti] Título: Analgesia evaluation of 2 NSAID drugs as adjuvant in management of chronic temporomandibular disorders. [So] Source: ScientificWorldJournal;2015:359152, 2015. [Is] ISSN: 1537-744X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The aim of this triple-blind full-randomized clinical trial was to quantify analgesia in masticatory muscles and temporomandibular joints after occlusal splint therapy associated with the adjuvant administration of nonsteroidal anti-inflammatory drugs (NSAID) isolated or associated with other therapeutic agents. Pain relief was also recorded. Eighteen volunteers who had been suffering from chronic pain in masticatory muscles due to temporomandibular disorders were selected after anamnesis and assessment using RDC/TMD translated to Portuguese. The 3 proposed treatments were NSAID (sodium diclofenac), panacea (sodium diclofenac + carisoprodol + acetaminophen + caffeine), and a placebo. The total treatment duration was 10 days, preceded and succeeded by patients' pain assessment. A washout interval of 11 days was established between each therapy. All participants received all treatments in different moments, in a full randomized crossover methodology. The assessment of drug therapies was performed using visual analogue scale for pain on palpation followed by 11-point numerical scale to quantify pain during treatment. Statistical analysis has shown that, after 10 days of treatment, all therapies were effective for pain relief. NSAID therapy promoted analgesia on the third day, while placebo only promoted analgesia in the eighth day. It has been concluded that sodium diclofenac used as splint adjuvant therapy, promotes significant analgesia in a shorter time. [Mh] Termos MeSH primário: Analgesia/métodos Anti-Inflamatórios não Esteroides/administração & dosagem Dor Crônica/tratamento farmacológico Manejo da Dor/métodos Medição da Dor/métodos Transtornos da Articulação Temporomandibular/tratamento farmacológico [Mh] Termos MeSH secundário: Acetaminofen/administração & dosagem Adulto Idoso Cafeína/administração & dosagem Carisoprodol/administração & dosagem Dor Crônica/diagnóstico Dor Crônica/epidemiologia Diclofenaco/administração & dosagem Método Duplo-Cego Quimioterapia Combinada Feminino Seres Humanos Masculino Meia-Idade Medição da Dor/efeitos dos fármacos Transtornos da Articulação Temporomandibular/diagnóstico Transtornos da Articulação Temporomandibular/epidemiologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); 144O8QL0L1 (Diclofenac); 21925K482H (Carisoprodol); 362O9ITL9D (Acetaminophen); 3G6A5W338E (Caffeine) [Em] Mês de entrada: 1607 [Cu] Atualização por classe: 150417 [Lr] Data última revisão: 150417 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 150416 [St] Status: MEDLINE [do] DOI: 10.1155/2015/359152

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[PMID]: 25324526 [Au] Autor: Knittel JL; Vorce SP; Levine B; Hughes RL; Bosy TZ [Ad] Endereço: Division of Forensic Toxicology, Armed Forces Medical Examiner System, Dover AFB, Dover, DE 19902, USA jessica.l.knittel.ctr@mail.mil. [Ti] Título: Multidrug toxicity involving sumatriptan. [So] Source: J Anal Toxicol;39(1):75-9, 2015 Jan-Feb. [Is] ISSN: 1945-2403 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: A multidrug fatality involving sumatriptan is reported. Sumatriptan is a tryptamine derivative that acts at 5-HT(1B/1D) receptors and is used for the treatment of migraines. The decedent was a 21-year-old white female found dead in bed by her spouse. No signs of physical trauma were observed and a large number of prescription medications were discovered at the scene. Toxicological analysis of the central blood revealed sumatriptan at a concentration of 1.03 mg/L. Following therapeutic dosing guidelines, sumatriptan concentrations do not exceed 0.095 mg/L. Sumatriptan was isolated by solid-phase extraction and analyzed using liquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode. A tissue distribution study was completed with the following concentrations measured: 0.61 mg/L in femoral blood, 0.56 mg/L in iliac blood, 5.01 mg/L in urine, 0.51 mg/kg in liver, 3.66 mg/kg in kidney, 0.09 mg/kg in heart, 0.32 mg/kg in spleen, 0.01 mg/kg in brain, 15.99 mg/kg in lung and 78.54 mg/45 mL in the stomach contents. Carisoprodol, meprobamate, fluoxetine, doxylamine, orphenadrine, dextromethorphan and hydroxyzine were also present in the blood at the following concentrations: 3.35, 2.36, 0.63, 0.19, 0.06, 0.55 and 0.16 mg/L. The medical examiner ruled the cause of death as acute mixed drug toxicity and the manner of death as accident. [Mh] Termos MeSH primário: Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/sangue Sumatriptana/envenenamento [Mh] Termos MeSH secundário: Autopsia Carisoprodol/sangue Cromatografia Líquida Dextrometorfano/sangue Doxilamina/sangue Estudos de Avaliação como Assunto Evolução Fatal Feminino Fluoxetina/sangue Toxicologia Forense Seres Humanos Hidroxizina/sangue Fígado/efeitos dos fármacos Fígado/metabolismo Meprobamato/sangue Orfenadrina/sangue Reprodutibilidade dos Testes Manejo de Espécimes Sumatriptana/farmacocinética Espectrometria de Massas em Tandem Distribuição Tecidual Adulto Jovem [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 01K63SUP8D (Fluoxetine); 21925K482H (Carisoprodol); 30S50YM8OG (Hydroxyzine); 7355X3ROTS (Dextromethorphan); 8R78F6L9VO (Sumatriptan); 95QB77JKPL (Doxylamine); 9I7LNY769Q (Meprobamate); AL805O9OG9 (Orphenadrine) [Em] Mês de entrada: 1510 [Cu] Atualização por classe: 150113 [Lr] Data última revisão: 150113 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 141018 [St] Status: MEDLINE [do] DOI: 10.1093/jat/bku120

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[PMID]: 25217546 [Au] Autor: Tiscione NB; Shan X; Yeatman DT [Ad] Endereço: Palm Beach County Sheriff's Office, 3228 Gun Club Road, West Palm Beach, FL 33406, USA tiscionen@pbso.org. [Ti] Título: Case management in a DUI lab: effect on drugs reported. [So] Source: J Anal Toxicol;38(8):555-8, 2014 Oct. [Is] ISSN: 1945-2403 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: An evaluation of an internal laboratory decision to implement a protocol for limiting drug testing based on ethanol concentration in laboratory analysis for driving under the influence (DUI) cases is presented. The described case management strategy is supported by known impairment of ethanol at relatively high concentrations, difficulty assigning a level of contributing impairment from drugs in the presence of high ethanol levels and the likelihood that the drug results may be suppressed at trial. Although the results of this study reinforce the assertion that such protocols lead to the under reporting of drugs in DUI cases, for the majority of cases, 95% in this study, the drug analysis results were not significant and did not warrant the time and resources needed for the additional blood drug testing. Furthermore, the study demonstrated that a high drug positivity rate does not necessarily mean that those drug results are legally or pharmacologically meaningful. Additional research should be conducted with quantitative drug results and casework impact of blood drug screen protocols as previous studies only report drug positivity rates and not whether the drug results would be meaningful to the case. [Mh] Termos MeSH primário: Condução de Veículo Etanol/sangue Toxicologia Forense/organização & administração Detecção do Abuso de Substâncias/métodos [Mh] Termos MeSH secundário: Barbitúricos/sangue Benzodiazepinas/sangue Carisoprodol/sangue Cocaína/análogos & derivados Cocaína/sangue Dronabinol/sangue Cromatografia Gasosa-Espectrometria de Massas Seres Humanos Metanfetamina/sangue Oxicodona/sangue Oximorfona/sangue [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Barbiturates); 12794-10-4 (Benzodiazepines); 21925K482H (Carisoprodol); 3K9958V90M (Ethanol); 44RAL3456C (Methamphetamine); 5353I8I6YS (benzoylecgonine); 7J8897W37S (Dronabinol); 9VXA968E0C (Oxymorphone); CD35PMG570 (Oxycodone); I5Y540LHVR (Cocaine) [Em] Mês de entrada: 1506 [Cu] Atualização por classe: 140913 [Lr] Data última revisão: 140913 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 140914 [St] Status: MEDLINE [do] DOI: 10.1093/jat/bku076

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