ANTAGONISM OF PULMONARY VASOCONSTRICTOR RESPONSE TO PROSTAGLANDIN-F2-ALPHA BY N-DIMETHYLAMINO SUBSTITUTION OF PROSTAGLANDIN-F2-ALPHA

  • 1 January 1978
    • journal article
    • research article
    • Vol. 206  (1) , 139-142
Abstract
Efforts to develop an in vivo prostaglandin (PG) antagonist have met with limited success. N-dimethylamino analogs of PGF2.alpha., which have proven to be effective in vitro prostaglandin antagonists, were tested for antagonism to the PGF2.alpha. and arachidonic acid (AA) responses in the canine lung lobe preparation. PGF2.alpha. (1 .mu.g/kg) and AA (100 .mu.g/kg) increased lobar arterial pressure by 54 and 83%, respectively. Infusion of analogs did not change lobar arterial pressure. N-dimethylamine PGF2.alpha. (0.8-3.2 .mu.g/ml) antagonized the PGF2.alpha. response by 66-79%. N-dimethylamide PGF2.alpha. (1.6-8.0 .mu.g/ml) produced a dose-dependent antagonism (24-75%) with an IC50 [median inhibitory concentration dosage] value of 3.8 .mu.g/ml. Neither analog significantly attenuated the pulmonary response to AA. These N-dimethylamino analogs of PGF2.alpha. exhibit a potency which is superior to previous in vivo prostaglandin antagonists. They have effectively differentiated the pulmonary vascular responses of AA and PGF2.alpha.