The effects of OP-1206 alpha-CD on walking dysfunction in the rat neuropathic intermittent claudication model.
IV prostaglandin E1 improves clinical symptoms in patients with spinal canal stenosis. In the present study, we assessed the effects of OP-1206 alpha-CD, an orally active prostaglandin E1 analog, on walking dysfunction in the rat neuropathic intermittent claudication model. To induce spinal stenosis, two pieces of silicon rubber were placed in the lumbar (L4-6) epidural space in rats. Postsurgical walking function was measured using a treadmill apparatus. Spinal cord blood flow (SCBF) and skin blood flow (SKBF) were measured using a laser-Doppler flowmeter. OP-1206 alpha-CD was administered orally bid for 11 days from postoperative Day 3. In Control nontreated rats, a significant walking dysfunction was observed from Day 1 after the induction of spinal stenosis and persisted for 14 days when compared with the Sham-Operated group. On postoperative Day 15, SCBF revealed a significant reduction in the territory of spinal stenosis, although SKBF was not affected. OP-1206 alpha-CD significantly improved walking dysfunction on postoperative Days 5 (300 microg/kg), 7 (150 and 300 microg/kg), and 14 (150 and 300 microg/kg) when compared with the Vehicle-Treated group. On postoperative Day 15, the decrease in SCBF was significantly (150 and 300 microg/kg) improved by OP-1206 alpha-CD treatment, albeit SKBF remained unaffected. These data show that oral treatment with OP-1206 alpha-CD is effective in improving walking dysfunction induced by spinal canal stenosis, and this therapeutic effect is likely mediated by improved SCBF at the territory of spinal stenosis.


CONCLUSIONS
Intermittent motor dysfunction is a clinical symptom associated with partial spinal compression. The present study provides evidence that oral treatment with the prostaglandin E1 analog (OP-1206 alpha-CD) is effective in improving motor dysfunction and spinal cord blood flow in rats with spinal compression.
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
Eguchi
Kazuhide
K
Takimizu
Hideyuki
H
Honjo
Kaneyoshi
K
Akimaru
Shinji
S
Maegawa
Hitoshi
H
Marsala
Martin
M
Katsube
Nobuo
N
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000818:Animals; D007383:Intermittent Claudication / Q000188:drug therapy*; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D013116:Spinal Cord / Q000098:blood supply / Q000187:drug effects; D013130:Spinal Stenosis / Q000503:physiopathology; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016138:Walking / Q000502:physiology*
D010975:Platelet Aggregation Inhibitors; D011459:Prostaglandins E, Synthetic; D014665:Vasodilator Agents; C025090:ONO 1206; D000527:Alprostadil