RESUMEN
OBJECTIVE: To report the demographic and clinical characteristics of cases of methoxetamine toxicity reported to The National Poisons Information Service (NPIS) by healthcare professionals. To assess the pattern of enquiries from health professionals to the UK NPIS related to methoxetamine, including the period of the making of the UK first Temporary Class Drug Order (TCDO). METHODS: All telephone enquiries to and user sessions for TOXBASE, the NPIS on-line information resource, related to methoxetamine (and synonyms 'MXE', 'mket' and '2-(3-methoxyphenyl)-2-(ethylamino)cyclohexanone') were reviewed from 1 April 2010 to 1 August 2012. Data were compared for the 3 months before and after the TCDO. RESULTS: There were 47 telephone enquiries and 298 TOXBASE sessions regarding methoxetamine during the period of study. Comparing the 3 months before and after the TCDO, TOXBASE sessions for methoxetamine fell by 79% (from 151 to 32) and telephone enquiries by 80% (from 15 to 3). Clinical features reported by enquirers were consistent with case reports of analytically confirmed methoxetamine toxicity and typical toxidromes were of stimulant (36%), reduced consciousness (17%), dissociative (11%) and cerebellar (6.4%) types, but also particularly featured acute disturbances in mental heath (43%). CONCLUSIONS: Structured NPIS data may reveal trends in drugs of abuse use and toxicity when interpreted within their limitations. Since April 2012, there have been fewer enquiries to NPIS from clinicians, indicating reduced presentations with suspected methoxetamine toxicity to healthcare services. It is unclear if this is related to the TCDO made on 5 April 2012.
Asunto(s)
Ciclohexanonas/toxicidad , Ciclohexilaminas/toxicidad , Ciclohexanonas/clasificación , Ciclohexilaminas/clasificación , Bases de Datos Factuales , Servicios de Información sobre Medicamentos , Trastornos Relacionados con Sustancias/epidemiología , Teléfono , Reino UnidoRESUMEN
Cyclophilins, which are found in all cellular compartments and with diverse biological roles, are now drug targets for a number of diseases including HIV infection, malaria and ischaemia. We used the database-mining program LIDAEUS and in silico screening to discover the dimedone family of inhibitors which show a conserved 'ball and socket' binding mode with a dimethyl group in the hydrophobic binding pocket of human cyclophilin A (CypA) mimicking a key interaction of the natural inhibitor cyclosporin A (CsA). The most potent derivative binds CypA with a K(d) of 11.2+/-9.2 microM and an IC50 for activity against Caenorhabditis elegans (C. elegans) of 190 microM compared to 28 microM for CsA. These dimedone analogues provide a new scaffold for the synthesis of families of peptidomimetic molecules with potential activity against HIV, malaria, and helminth parasite infections.
Asunto(s)
Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/enzimología , Ciclohexanonas/química , Ciclohexanonas/farmacología , Ciclofilina A/antagonistas & inhibidores , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Animales , Cristalografía por Rayos X , Ciclohexanonas/síntesis química , Ciclohexanonas/clasificación , Ciclofilina A/química , Ciclofilina A/metabolismo , Ciclosporina/química , Ciclosporina/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/clasificación , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Estructura Molecular , Fenotipo , Unión Proteica , Relación Estructura-ActividadRESUMEN
A database on UV-absorbing mycosporines and mycosporine-like amino acids (MAAs) has been constructed that provides information on various mycosporines and MAAs reported in fungi, cyanobacteria, macroalgae, phytoplankton and animals from aquatic and terrestrial habitats. It also contains information on biosynthetic routes of MAAs as well as on the absorption maxima and molecular structures of different mycosporines and MAAs (Table 1S). This database provides necessary information for scientists working in the field of photoprotective compounds in fungi, cyanobacteria, macroalgae, phytoplankton and animals (Table 2S). (Tables 1S and 2S are available online as Supplementary material in the electronic copy of the journal as well as on our server