The systemic treatment effects of
OP-1206 alpha-CD (17S-20-dimethyl-trans-delta 2-PGE1 alpha-cyclodextrin clathrate), a
prostaglandin E1 (
PGE1) analogue, on walking dysfunction, spinal cord blood flow (SCBF) and skin blood flow (SKBF) were assessed in the rat neuropathic
intermittent claudication (IC) model in comparison with
nifedipine (dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate),
ticlopidine (5-[(2-chlorophenyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-C]
pyridine hydrochloride) and
cilostazol (6-[4-(1-cyclohexyl-1H-tetrazol-5-yl)-butoxy]-3,4-dihydro-2(1H)-
quinolinone). Two pieces of
silicone rubber strips were placed in the lumbar (L4 and L6) epidural space in rats. After surgery, walking function was measured using a treadmill apparatus. SCBF and SKBF were measured using a
laser-Doppler flow meter. Drugs were administered orally twice a day for 11 days from day 3 post-surgery. Treatment with
OP-1206 alpha-CD significantly improved walking dysfunction on days 5, 7 and 14, and improved SCBF on day 14 post-surgery. SKBF remained unaffected. Treatment with
nifedipine,
ticlopidine or
cilostazol had no significant effects on any of the parameters measured in this model. These data suggest that the
therapeutic effect of
OP-1206 alpha-CD is primarily mediated by the improved local SCBF at the territory of
spinal stenosis and not due to improvement of peripheral perfusion and/or antiplatelet activity.