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dc.contributor.authorSneyd, JRen
dc.contributor.authorRigby-Jones, AEen
dc.contributor.authorCross, Men
dc.contributor.authorTominaga, Hen
dc.contributor.authorShimizu, Sen
dc.contributor.authorOhkura, Ten
dc.contributor.authorGrimsehl, Ken
dc.date.accessioned2012-11-09T22:18:14Z
dc.date.available2012-11-09T22:18:14Z
dc.date.issued2012-02en
dc.identifier.urihttp://hdl.handle.net/10026.1/1226
dc.description.abstract

BACKGROUND: JM-1232(-), (-)-3-[2-(4-methyl-1-piperazinyl)-2-oxoethyl]-2-phenyl-3,5,6,7-tetrahydrocyclopenta [f]isoindol-1(2H)-one, molecular formula, C(24)H(27)N(3)O(2); molecular weight, 389.49, is a novel isoindoline water-soluble benzodiazepine receptor agonist with favorable anesthetic/sedative properties in animals. MR04A3 is a 1% aqueous presentation of JM-1232(-). METHODS: In Step 1, healthy male volunteers received 10-min infusions of MR04A3, 0.05, 0.1, 0.2, 0.4, and 0.8 mg/kg, with three MR04A3 subjects and one placebo subject per dose concentration. In Step 2, doses were 0.025, 0.05, 0.075, 0.1, 0.2, 0.3, and 0.4 mg/kg over 1 min with six MR04A3 subjects and one placebo subject per dose concentration. RESULTS: Hypnotic effects of MR04A3 were seen at all dose concentrations in Step 1 and at doses of 0.075 mg/kg or more in Step 2. Central nervous system effect was seen at all dose concentrations with larger doses of MR04A3 producing a deeper and longer reduction in bispectral index. Ramsay sedation scores were increased with higher doses causing sedation and then unresponsiveness. The adverse event profile of subjects receiving MR04A3 was similar to that of subjects given placebo except that some subjects receiving MR04A3 developed upper airway obstruction while sedated. This responded to simple maneuvers (i.e., chin lift). Changes in systolic arterial blood pressure and heart rate were minimal. CONCLUSIONS: MR04A3 is hypnotic in man with a satisfactory hemodynamic and safety profile.

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dc.format.extent385 - 395en
dc.languageengen
dc.language.isoengen
dc.subjectAdolescenten
dc.subjectAdulten
dc.subjectBenzodiazepinesen
dc.subjectDose-Response Relationship, Drugen
dc.subjectHumansen
dc.subjectHypnotics and Sedativesen
dc.subjectIsoindolesen
dc.subjectMaleen
dc.subjectPiperazinesen
dc.subjectSolubilityen
dc.subjectWateren
dc.subjectYoung Adulten
dc.titleFirst human administration of MR04A3: a novel water-soluble nonbenzodiazepine sedative.en
dc.typeJournal Article
plymouth.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/22222479en
plymouth.issue2en
plymouth.volume116en
plymouth.publication-statusPublisheden
plymouth.journalAnesthesiologyen
dc.identifier.doi10.1097/ALN.0b013e318242b2afen
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
plymouth.organisational-group/Plymouth/Users by role/Professional Services staff
dc.publisher.placeUnited Statesen
dc.identifier.eissn1528-1175en
dc.rights.embargoperiodNot knownen
rioxxterms.versionofrecord10.1097/ALN.0b013e318242b2afen
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.typeJournal Article/Reviewen


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