{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:20:07Z","timestamp":1787318407528,"version":"build-2736575974"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,11,20]],"date-time":"2013-11-20T00:00:00Z","timestamp":1384905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2013,12]]},"abstract":"\n Aim<\/jats:title>\n \n Cannabinoid receptor type 1 (\n CB<\/jats:styled-content>\n 1<\/jats:sub>\n ) antagonists show central side effects, whereas beneficial effects are most likely peripherally mediated. In this study, the peripherally selective\n CB<\/jats:styled-content>\n 1<\/jats:sub>\n antagonist\n TM<\/jats:styled-content>\n 38837 was studied in humans.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This was a double\u2010blind, randomized, placebo\u2010controlled, crossover study. On occasions 1\u20134, 24 healthy subjects received 5 \u00d7 4\u2009mg\n THC<\/jats:styled-content>\n with\n TM<\/jats:styled-content>\n 38837 100\u2009mg, 500\u2009mg or placebo, or placebos only. During occasion 5, subjects received placebo\n TM<\/jats:styled-content>\n 38837 +\n THC<\/jats:styled-content>\n with rimonabant 60\u2009mg or placebo in parallel groups. Blood collections and pharmacodynamic (\n PD<\/jats:styled-content>\n ) effects were assessed frequently. Pharmacokinetics (\n PK<\/jats:styled-content>\n ) and\n PD<\/jats:styled-content>\n were quantified using population\n PK<\/jats:styled-content>\n \u2212\n PD<\/jats:styled-content>\n modelling.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n TM<\/jats:styled-content>\n 38837 plasma concentration profile was relatively flat compared with rimonabant.\n TM<\/jats:styled-content>\n 38837 showed an estimated terminal half\u2010life of 771\u2009h.\n THC<\/jats:styled-content>\n induced effects on\n VAS<\/jats:styled-content>\n feeling high, body sway and heart rate were partly antagonized by rimonabant 60\u2009mg [\u221226.70% [90% confidence interval (CI) \u221240.9, \u221212.6%]; \u22127.10%, (90%\n CI<\/jats:styled-content>\n \u221218.1, 5.3%); \u22127.30%, (90%\n CI<\/jats:styled-content>\n \u221211.5%, \u22123.0%) respectively] and\n TM<\/jats:styled-content>\n 38837 500\u2009mg [\u221222.10% (90%\n CI<\/jats:styled-content>\n \u221234.9, \u22129.4%); \u221212.20% (90%\n CI<\/jats:styled-content>\n \u221221.6%, \u22121.7%); \u22128.90% (90%\n CI<\/jats:styled-content>\n \u221212.8%, \u22125.1%) respectively].\n TM<\/jats:styled-content>\n 38837 100\u2009mg had no measurable feeling high or body sway effects and limited heart rate effects.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Rimonabant showed larger effects than\n TM<\/jats:styled-content>\n 38837, but the heart rate effects were similar.\n TM<\/jats:styled-content>\n 38837 100\u2009mg had no impact on\n CNS<\/jats:styled-content>\n effects, suggesting that this dose does not penetrate the brain. This\n TM<\/jats:styled-content>\n 38837 dose is predicted to be at least equipotent to rimonabant with regard to metabolic disorders in rodent models. These results provide support for further development of\n TM<\/jats:styled-content>\n 38837 as a peripherally selective\n CB<\/jats:styled-content>\n 1<\/jats:sub>\n antagonist for indications such as metabolic disorders, with a reduced propensity for psychiatric side effects.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/bcp.12141","type":"journal-article","created":{"date-parts":[[2013,4,19]],"date-time":"2013-04-19T04:12:38Z","timestamp":1366344758000},"page":"846-857","source":"Crossref","is-referenced-by-count":75,"title":["Peripheral selectivity of the novel cannabinoid receptor antagonist\n TM<\/scp>\n 38837 in healthy subjects"],"prefix":"10.1111","volume":"76","author":[{"given":"Linda E.","family":"Klumpers","sequence":"first","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Fridberg","sequence":"additional","affiliation":[{"name":"7TM Pharma Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke L.","family":"de Kam","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul B.","family":"Little","sequence":"additional","affiliation":[{"name":"7TM Pharma Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels Ole","family":"Jensen","sequence":"additional","affiliation":[{"name":"7TM Pharma Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hendrik D.","family":"Kleinloog","sequence":"additional","affiliation":[{"name":"Centre for Human Drug Research Leiden the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian E.","family":"Elling","sequence":"additional","affiliation":[{"name":"7TM Pharma Lyngby Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joop M. 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