Efficacy and tolerability of a selective alpha(2C)-adrenergic receptor blocker in recovery from cold-induced vasospasm in scleroderma patients: a single-center, double-blind, placebo-controlled, randomized crossover study

Arthritis Rheum. 2004 Dec;50(12):3994-4001. doi: 10.1002/art.20665.


Objective: OPC-28326 is a selective alpha-adrenergic antagonist with preferential binding to the alpha(2C)-adrenergic receptor (alpha(2C)-AR) subtype. This study observed the effect of OPC-28326 on skin temperature and digital blood flow following an acute cold challenge in patients with Raynaud's phenomenon secondary to scleroderma.

Methods: The study was designed as a single-center, double-blind, placebo-controlled, randomized, 3-period crossover study of OPC-28326 (oral doses of 10 mg or 40 mg) or placebo. The primary outcome measures were the time to recover 50% and 70% of the fall (induced by cold challenge) in baseline digital skin temperature.

Results: Twelve of 13 enrolled patients completed the study. The mean time to achieve 50% and 70% recovery of the change in prechallenge digital skin temperature was shorter after the OPC-28326 40-mg dose than after placebo (50% recovery at 5.8 minutes versus 10.0 minutes [P = 0.02]; 70% recovery at 13.8 minutes versus 19.5 minutes [P = 0.01]). These recovery times tended to be shorter in the 10 mg OPC-28326 group as well, but the difference versus placebo was not significant (50% recovery at 9.0 minutes versus 10.0 minutes [P = 0.65]; 70% recovery at 15.3 minutes versus 19.5 minutes [P = 0.07]). Total digital blood flow tended to be lower prior to the cold challenge and after administration of 40 mg OPC-28326, as compared with that after placebo, but the difference was not significant. Symptoms that were potentially drug-related were reported more frequently with 40 mg OPC-28326 than with 10 mg OPC-28326 or with placebo, but none were serious or sustained.

Conclusion: OPC-28326 at doses of 10 mg and 40 mg was well tolerated during this study. The shorter time to skin temperature recovery after 40 mg OPC-28326 suggests that selective alpha(2C)-AR blockade improves digital skin perfusion during recovery from cooling in patients with Raynaud's phenomenon secondary to scleroderma.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adrenergic alpha-Antagonists / administration & dosage
  • Adrenergic alpha-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Aniline Compounds / administration & dosage
  • Aniline Compounds / therapeutic use*
  • Cold Temperature / adverse effects
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fingers / blood supply
  • Humans
  • Male
  • Middle Aged
  • Piperidines / administration & dosage
  • Piperidines / therapeutic use*
  • Raynaud Disease / drug therapy*
  • Raynaud Disease / etiology
  • Raynaud Disease / physiopathology
  • Regional Blood Flow / drug effects
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / drug therapy*
  • Scleroderma, Systemic / physiopathology
  • Skin Temperature / drug effects*
  • Vasodilation / drug effects


  • Adrenergic alpha-Antagonists
  • Aniline Compounds
  • Piperidines
  • OPC 28326