Studies on WF-3681, a novel aldose reductase inhibitor. IV. Effect of FR-62765, a derivative of WF-3681, on the diabetic neuropathy in rats.
Pharmacokinetic properties of WF-3681 and FR-62765 in rats were examined. FR-62765 showed higher peak concentrations in the plasma and higher concentrations in the sciatic nerve than WF-3681 when each compound was administered orally to rats. We therefore evaluated FR-62765 in rats with diabetic neuropathy. As a result, FR-62765 at 32 mg/kg/day administered for 3 weeks to streptozotocin-induced diabetic rats significantly prevented the accumulation of sorbitol in the sciatic nerve and the reduction of motor nerve conduction velocity in the tail. From these results it was concluded that the aldose reductase inhibitor FR-62765 might be a useful drug for diabetic neuropathy.
Nishikawa
M
M
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Ibaraki, Japan.
Yoshida
K
K
Okamoto
M
M
Itoh
Y
Y
Kohsaka
M
M
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D005663:Furans / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000378:metabolism; D013012:Sorbitol / Q000378:metabolism
D005663:Furans; C068897:FR 62765; C054351:WF 3681; D013012:Sorbitol; D000449:Aldehyde Reductase