The alpha (1D)-adrenoceptor antagonist BMY 7378 is also an alpha (2C)-adrenoceptor antagonist

Auton Autacoid Pharmacol. 2005 Oct;25(4):135-41. doi: 10.1111/j.1474-8673.2005.00342.x.

Abstract

1 We have investigated the actions of the alpha(1D)-adrenoceptor selective antagonist BMY 7378 in comparison with yohimbine at alpha(1)- and alpha(2)-adrenoceptors. 2 In rat aorta (alpha(1D)-adrenoceptor), BMY 7378 (pA(2) of 8.67) was about 100 times more potent than yohimbine (pA(2) of 6.62) at antagonizing the contractile response to noradrenaline. 3 In human saphenous vein (alpha(2C)-adrenoceptor), BMY 7378 (pA(2) of 6.48) was approximately 10 times less potent than yohimbine (pA(2) of 7.56) at antagonizing the contractile response to noradrenaline. 4 In prostatic portions of rat vas deferens, BMY 7378 (10 mum) did not significantly affect the concentration-dependent inhibition of single pulse nerve stimulation-evoked contractions by xylazine (an action at prejunctional alpha(2D)-adrenoceptors). 5 In ligand-binding studies, BMY 7378 showed 10-fold selectivity for alpha(2C)-adrenoceptors (pK(i) of 6.54) over other alpha(2)-adrenoceptors. 6 It is concluded that BMY 7378, in addition to alpha(1D)-adrenoceptor selectivity in terms of alpha(1)-adrenoceptors, shows selectivity for alpha(2C)-adrenoceptors in terms of alpha(2)-adrenoceptors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic alpha-1 Receptor Antagonists*
  • Adrenergic alpha-2 Receptor Antagonists*
  • Adrenergic alpha-Antagonists / pharmacology*
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • In Vitro Techniques
  • Ligands
  • Male
  • Piperazines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Adrenergic, alpha-2 / metabolism
  • Saphenous Vein / drug effects
  • Saphenous Vein / metabolism
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism
  • Yohimbine / pharmacology

Substances

  • ADRA1D protein, human
  • ADRA2C protein, human
  • Adra1d protein, rat
  • Adra2c protein, rat
  • Adrenergic alpha-1 Receptor Antagonists
  • Adrenergic alpha-2 Receptor Antagonists
  • Adrenergic alpha-Antagonists
  • Ligands
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • Receptors, Adrenergic, alpha-2
  • Yohimbine
  • BMY 7378