SDZ NVI 085, an alpha 1A-adrenoceptor agonist with 5-HT2A receptor antagonist properties

Eur J Pharmacol. 1996 Feb 15;297(1-2):83-6. doi: 10.1016/0014-2999(95)00850-0.

Abstract

(+/-)-SDZ NVI 085 (3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9- methylthio-2H-naphth [2,3-b]-1,4-oxazine hydrochloride), an alpha 1-adrenoceptor agonist, produced a concentration-dependent relaxation (pIC50 of 7.2 +/- 0.1) in the isolated caudal artery of rat precontracted with serotonin (5-hydroxytryptamine, 5-HT, 1 microM). (+/-)- SDZ NVI 085 had no effect upon caudal arteries precontracted with vasopressin or U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxymethano-prostaglandin F2 alpha). In other studies, (+/-)-SDZ NVI 085 shifted 5-HT concentration-effect curves to the right, in a concentration-dependent manner, and Schild regression gave a pA2 estimate of 8.0 (slope of 1.0). Experiments using pharmacological resultant analysis indicated a syntopic interaction of (+/-)-SDZ NVI 085 with ketanserin (a 5-HT2 receptor antagonist) toward 5-HT-induced contractions. It is concluded that (+/-)-SDZ NVI 085 behaves as a reversible competitive 5-HT2A receptor antagonist, a property which may be of importance regarding its pharmacological effects in vivo.

MeSH terms

  • Adrenergic alpha-1 Receptor Agonists*
  • Adrenergic alpha-Agonists / pharmacology*
  • Adrenergic alpha-Antagonists / pharmacology
  • Animals
  • Bridged-Ring Compounds / pharmacology*
  • Idazoxan / pharmacology
  • Ketanserin / pharmacology
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Oxazines / pharmacology*
  • Prazosin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Serotonin / drug effects*
  • Regional Blood Flow / drug effects
  • Serotonin Antagonists / pharmacology*
  • Tail / blood supply

Substances

  • Adrenergic alpha-1 Receptor Agonists
  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Bridged-Ring Compounds
  • Oxazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • SDZ NVI-085
  • Ketanserin
  • Prazosin
  • Idazoxan