[The vasodilation effects of flokalin, a fluorine-containing K(ATP) channel opener].
In experiments on anesthetized dogs it was shown that the amplitude and duration of hypotensive effect of flocalin, a fluorine-containing pinacidil analogue, were dose-dependent and similar to those evoked by the known ATP-sensitive potassium channel opener pinacidil. However, flocalin appeared to be 3.5 times less toxic than pinacidil. Registration of systemic arterial pressure (SAP) has shown that following intravenous introduction of the threshold dose of flocalin (0.05 mg/ kg) the dilatation lasts around three minutes with the amplitude 9.52% +/- 2.01% (n=7, P < 0.05). Introduction of flocalin in a dose 0.5 mg/kg and above reduced SAP on more than 37%. Flocalin at 0.5, 0.75, 1.0 and 1.5 mg/kg reduced SAP by 42.07 +/- 6.18 (n=5, P < 0.05); 44.22 +/- 4.87 (n=3, P < 0.05); 44.3 +/- 4.59 (n=5, P < 0.05) and 66.28 +/- 3.15 mm Hg (n=3, P < 0.05), accordingly. Intravenous introduction of high doses of flocalin (0.75-1.5 mg/kgs) quite often reduced SAP to 40-50 mm Hg. However, such dangerous reduction in arterial pressure was comparatively short and lasted not more than 15 minutes, and then (usually within an hour) SAP gradually restored. Introduction of flocalin in hip artery, while measuring the perfusion pressure, produced practically similar results. In our opinion, the optimal cardioprotective doses of flocalin were 0.1 and 0.2 mg/kg. In experiments with acute ischemia and reperfusion of myocardium, preischemic introduction of flocalin at 0.1 and 0.2 mg/kg reduced an infarct size of myocardium by 37-40% and reduced SAP within first 5 and 25 minutes, accordingly.
Strutyns'kyĭ
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D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005461:Fluorine / Q000737:chemistry*; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D015640:Ion Channel Gating / Q000187:drug effects*; D054086:KATP Channels / Q000819:agonists*; D008297:Male; D020110:Pinacidil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*
D054086:KATP Channels; C559719:N-(4-difluoromethoxyphenyl)-N'-pinacolyl-N''-cyanoguanidine; D014665:Vasodilator Agents; D005461:Fluorine; D020110:Pinacidil