Vascular and platelet pharmacology of 2‐camphanone, a new drug for the treatment of hemorrhoids

Abstract

Abstract2‐Camphanone (Alphanon ®) is under clinical evaluation for the treatment of hemorrhoids. This study examined the effect of 2‐camphanone on three parameters affecting hemorrhoidal distention: portal venous blood flow, vascular smooth muscle tone, and aggregation of human platelets. Mongrel dogs (10–18 kg) of either sex were anesthetized with pentobarbital sodium (35 mg/kg, i.v.) and instrumented for doppler measurment of portal vein and and fermoral artery blood flow velocity using a closed‐chest, spontaneusly breathing preparation. Intravenous. (i.v.) administration of 2‐camphanone (0.01, 0.03, 0.1, 0.3, and 0.6 mg/kg) or transdermal administration of 6 mg of 2‐camphanone selectively increased portal venous blood flow velocity by 13–31% above pre‐drug control values. 2‐Camphanone (0.1 to 100 μM) produced endothelium‐dependent relaxation of canine portal‐mesenteric (MV) and portal veins (PV), but not mesenteric arteries (MA), pre‐contracted with an EC50 concentration of norepinephrine (NE). 2‐Camphanone also inhibited acetylcholine‐induced contraction of MV but did not affect the contraction of the MV to NE, nerve stimulation, or KCl. The inhibitory effect of 2‐camphanone was not stereo‐sepcific but resided in both the (+) and (−)isomers. 2‐camphanone (up to 1 mM) did not affect platelet aggregation produced by ADP, collagen, or arachidonic acid, but inhibited epinephrine‐induced aggregation. The results show that 2‐camphanone increases portal venous blood flow velocity. 2‐Camphanone is effective by the i.v. and transdermal routes of administration. The effect may be mediated by substances released from the venous endothelium. Speculatively, this may reflect a free radical scavenging or anti‐oxidant effect of 2‐camphanone. This may be aided, in part, by camphanone‐induced inhibition of epinephrine‐mediated release of plateletderived venous stimulants during the stressful hemorrhoidal episodes.