OPC-28326, a selective femoral vasodilator, is an alpha2C-adrenoceptor-selective antagonist.

Abstract

OPC-28326 has been reported to selectively increase femoral blood flow in open-chest dogs and autoperfused canine femoral artery preparations. Preliminary data indicated that OPC-28326 has a high affinity at the alpha2-adrenoceptor. In the present study, we tested OPC-28326 in isoflurane anesthetized rats at a dose of 3 mg/kg of body weight, given intraduodenally. OPC-28326 significantly increased femoral blood flow, by 44.7 +/- 13.8%, 45 min after drug administration, whereas carotid blood flow increased by only 3.6 +/- 5.5% (n = 6). Chinese hamster ovary cell lines overexpressing rat alpha2D-, alpha2B-, or alpha2C-adrenoceptor were established. These cells also coexpress luciferase, driven by cAMP elevation. In radioligand binding assays using cell membrane preparations, OPC-28326 dose dependently competed with [3H]RX821002 binding, with calculated K(i) values of 3840 +/- 887, 633 +/- 46, and 13.7 +/- 1.9 nM on alpha2D-, alpha2B-, and alpha2C-adrenoceptor, respectively. A similar affinity and rank order of potency were also found for OPC-28326 on the alpha2-subtypes using epinephrine as agonist in luciferase assays. No agonistic effect of OPC-28326 was detected on any of the alpha2-adrenoceptors. Finally, in situ hybridization performed on skeletal muscle tissue sections collected from rat hind limb (musculus gastrocnemius) demonstrated a high level expression of alpha2C in the vascular tissues. Thus, the abundance of alpha2C in the skeletal muscle may account for the selective effect of OPC-28326 in increasing femoral blood flow.

• Authors: B Sun, S Lockyer, J Li, R Chen, M Yoshitake, J I Kambayashi
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 299 Issue 2 Pg. 652-8 (Nov 2001) ISSN: 0022-3565 [Print] United States
• PMID: 11602678 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Antagonists
• Aniline Compounds
• Piperidines
• Vasodilator Agents
• Yohimbine
• Luciferases
• Alprostadil
• OPC 28326

Topics

• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Antagonists (pharmacology)
• Alprostadil (pharmacology)
• Aniline Compounds (pharmacology)
• Animals
• CHO Cells
• Cloning, Molecular
• Cricetinae
• Femoral Vein (drug effects)
• Hindlimb (drug effects)
• In Situ Hybridization
• In Vitro Techniques
• Luciferases (metabolism)
• Male
• Piperidines (pharmacology)
• Radioligand Assay
• Rats
• Rats, Sprague-Dawley
• Regional Blood Flow (drug effects)
• Vasodilator Agents (pharmacology)
• Yohimbine (pharmacology)