Effects of orally administered OP-1206 alpha-CD with loxoprofen-Na on walking dysfunction in the rat neuropathic intermittent claudication model.
An orally active prostaglandin E1 analogue, OP-1206 alpha-CD improves walking dysfunction in the rat spinal stenosis model. Loxoprofen-Na, a non-steroidal anti-inflammatory drug, is used to relieve chronic pain in patients with lumbar spinal canal stenosis. To determine whether the OP-1206 alpha-CD in combination with loxoprofen-Na could induce a greater therapeutical effect on walking dysfunction and spinal cord blood flow (SCBF) than OP-1206 alpha-CD treatment alone after chronic spinal stenosis in the rat. Spinal stenosis was induced by placing two pieces of silicon rubber strips in the lumbar (L4 and L6) epidural space of rats. After surgery, walking function was measured using a treadmill apparatus and SCBF was measured using a laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from the day 3 post-surgery. OP-1206 alpha-CD elicited a significant improvement of walking dysfunction on days 7 and 14 post-surgery and significantly increased spinal cord blood flow on day 15, whereas walking dysfunction and SCBF of rats treated with loxoprofen-Na alone remained unchanged. Combined treatment of OP-1206 alpha-CD with loxoprofen-Na did not provide additive therapeutical effect. These results suggest that a significant improvement seen after OP-1206 alpha-CD treatment is primarily mediated by improvement of the local spinal cord blood flow. This effect is not ameliorated or potentiated by a combined treatment with loxoprofen-Na.
Nakai
Katsuhiko
K
Discovery Research Laboratories III, Minase Research Institute, Ono Pharmaceutical Co. Ltd., 3-1-1 Sakurai, Shimamoto-cho, Mishima-gun, Osaka 618-8585, Japan.
Takenobu
Yoshifumi
Y
Takimizu
Hideyuki
H
Akimaru
Shinji
S
Ito
Hidenori
H
Maegawa
Hitoshi
H
Marsala
Martin
M
Katsube
Nobuo
N
D000284:Administration, Oral; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D003505:Cyclodextrins; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D007383:Intermittent Claudication / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010666:Phenylpropionates / Q000008:administration & dosage / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply; D013130:Spinal Stenosis / Q000188:drug therapy / Q000503:physiopathology; D016138:Walking; D047391:alpha-Cyclodextrins
D003505:Cyclodextrins; D010666:Phenylpropionates; D011459:Prostaglandins E, Synthetic; D047391:alpha-Cyclodextrins; C040656:loxoprofen; C025090:ONO 1206; D000527:Alprostadil; C032613:alpha-cyclodextrin