{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:39:40Z","timestamp":1780461580674,"version":"3.54.1"},"reference-count":48,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2020,2,3]],"date-time":"2020-02-03T00:00:00Z","timestamp":1580688000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2020,4]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>HM01, a novel, orally bioavailable, brain\u2010penetrating agonist of ghrelin receptors, ameliorates emesis in <jats:styled-content style=\"fixed-case\"><jats:italic>Suncus murinus<\/jats:italic><\/jats:styled-content>. This study compared HM01's activity against motion sickness with that of the less brain\u2010penetrating ghrelin receptor agonist, HM02.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The potential of HM01 and HM02 to relax isolated mesenteric arteries and to increase feeding was investigated. Radio telemetry was used to record gastric slow waves and body temperature. Plethysmography was used to measure respiratory function. HM01 and HM02 were administered p.o. 1 hr prior to provocative motion, and c\u2010Fos expression in brain sections was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>HM01 and HM02 both relaxed precontracted arteries, yielding EC<jats:sub>50<\/jats:sub> values of 2.5 \u00b1 0.5 and 3.5 \u00b1 0.4 nM respectively. HM01 increased feeding, but HM02 did not. Both compounds caused hypothermia and bradygastria. Motion induced 123 \u00b1 24 emetic events. HM01, but not HM02, reduced motion\u2010induced emesis by 67.6%. Motion increased c\u2010Fos expression in the nucleus tractus solitarius (NTS), dorsal motor nucleus of the vagus (DMNV), medial vestibular nucleus (MVe), central nucleus of the amygdala, and paraventricular hypothalamic nucleus (PVH). HM01 alone increased c\u2010Fos expression in the area postrema, NTS, DMNV, PVH, and arcuate hypothalamic nucleus; HM02 had a similar pattern except it did not increase c\u2010Fos in the PVH. Both compounds antagonized the motion\u2010induced increases in c\u2010Fos expression in the MVe.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>HM01 is more effective than HM02 in preventing motion\u2010induced emesis. The difference in potency may relate to activation of ghrelin receptors in the PVH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14924","type":"journal-article","created":{"date-parts":[[2019,11,13]],"date-time":"2019-11-13T23:13:55Z","timestamp":1573686835000},"page":"1635-1650","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The brain\u2010penetrating, orally bioavailable, ghrelin receptor agonist HM01 ameliorates motion\u2010induced emesis in <scp><i>Suncus murinus<\/i><\/scp> (house musk shrew)"],"prefix":"10.1111","volume":"177","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-6002","authenticated-orcid":false,"given":"Longlong","family":"Tu","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zengbing","family":"Lu","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man P.","family":"Ngan","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis F.Y.","family":"Lam","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Giuliano","sequence":"additional","affiliation":[{"name":"Research and Preclinical Development Department Helsinn Healthcare SA  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Lovati","sequence":"additional","affiliation":[{"name":"Research and Preclinical Development Department Helsinn Healthcare SA  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Pietra","sequence":"additional","affiliation":[{"name":"Research and Preclinical Development Department Helsinn Healthcare SA  Lugano Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8316-0792","authenticated-orcid":false,"given":"John A.","family":"Rudd","sequence":"additional","affiliation":[{"name":"School of Biomedical Sciences The Chinese University of Hong Kong  Shatin Hong Kong"},{"name":"The Laboratory Animal Services Centre The Chinese University of Hong Kong  Shatin Hong Kong"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14748"},{"key":"e_1_2_11_3_1","volume-title":"Management of chemotherapy\u2010induced nausea and vomiting: New agents and new uses of current agents","author":"Andrews P. 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