{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:12:34Z","timestamp":1745554354802,"version":"3.40.4"},"reference-count":4,"publisher":"S. Karger AG","issue":"3","license":[{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[1998,1,1]],"date-time":"1998-01-01T00:00:00Z","timestamp":883612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[1998]]},"abstract":"<jats:p>The cardiovascular effects of SKP-450, a newly synthesized potassium channel activator, and its two major metabolites SKP-818 and SKP-310 were evaluated on isolated rat aorta and in freely moving rats and anesthetized beagle dogs. The rank order of potency in relaxing rat aorta precontracted with norepinephrine was SKP-450&gt;SKP-818&gt;lemakalim&gt;SKP-310 (EC&lt;sub&gt;50&lt;\/sub&gt;: 0.12, 0.55, 0.71 and 5.89\u00a0\u00b5mol\/l, respectively). In rats, SKP-450, SKP-818 and lemakalim (3\u2013100\u00a0\u00b5g\/kg, i.v.) induced a dose-dependent decrease in mean arterial pressure (MAP; ED&lt;sub&gt;20&lt;\/sub&gt;: 9.8, 11.7 and 22.4\u00a0\u00b5g\/kg, respectively) followed by reflex tachycardia. In dogs, SKP-818 and SKP-310 (0.3\u20131,000\u00a0\u00b5g\/kg, i.v.) had quite similar hemodynamic profiles to SKP-450 but with a smaller potency. SKP-450, SKP-818 and SKP-310 dose-relatedly decreased MAP (ED&lt;sub&gt;20&lt;\/sub&gt;: 2.6, 4.2 and 588.8\u00a0\u00b5g\/kg, respectively). They slightly increased left ventricular positive dP\/dt&lt;sub&gt;max&lt;\/sub&gt; with a transient decrease at the highest dose, while inducing a dose-related decrease in rate-pressure product, tension time index and systolic time. SKP-450, SKP-818 and SKP-310 induced a marked dose-dependent increase in coronary blood flow (E&lt;sub&gt;max&lt;\/sub&gt;: 172.8, 257.9 and 178.7%, respectively) with less effects on blood flow through other arteries. Glybenclamide antagonized all the hemodynamic effects of SKP-450 in rats and dogs, whereas propranolol antagonized its reflex tachycardia in rats. These results indicate that SKP-450 is a potent coronary and peripheral vasodilator in rats and dogs activating ATP-sensitive potassium channels and that SKP-818 and SKP-310 exert a similar hemodynamic profile to the parent compound with equi- and weaker potency, respectively.<\/jats:p>","DOI":"10.1159\/000028188","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T13:07:10Z","timestamp":1050412030000},"page":"111-124","source":"Crossref","is-referenced-by-count":8,"title":["Cardiovascular Pharmacology of SKP-450, a New Potassium Channel Activator, and Its Major Metabolites SKP-818 and SKP-310"],"prefix":"10.1159","volume":"56","author":[{"given":"Hwa Sup","family":"Shin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ho Won","family":"Seo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung Eun","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byung Ho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[1998,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(88)90238-6"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1016\/0306-3623(89)90052-9"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90659-7"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(90)90342-O"}],"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/28188","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/28188","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T04:14:15Z","timestamp":1745468055000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000028188"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1998]]},"references-count":4,"journal-issue":{"issue":"3","published-online":{"date-parts":[[1998,3,1]]}},"URL":"https:\/\/doi.org\/10.1159\/000028188","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"type":"print","value":"0031-7012"},{"type":"electronic","value":"1423-0313"}],"subject":[],"published":{"date-parts":[[1998]]}}}