2-decarboxy-2-hydroxymethyl prostaglandin E1 (TR4161), a prostaglandin bronchodilator of low tracheobronchial irritancy.
2-Decarboxy 2-hydroxymethyl prostaglandin E1 (TR4161) relaxed isolated quinea-pig trachea with about double and relaxed human isolated bronchial muscle with about one half the potency of PGE1. In conscious restrained cats an aerosol of TR4161 was about 100-1000 times less active than PGE1 in inducing tracheobronchial irritation. When given intravenously or by aerosol to the anaesthetised spontaneously breathing guinea-pig, TR4161 was approximately equipotent with PGE1 in inhibiting histamine-induced bronchoconstriction and in reducing basal inherent tone. The onset and duration of the bronchodilator effects of TR4161 administered intravenously, however, were significantly longer than those of PGE1. In conscious quinea-pigs, TR4161 by aerosol was approximately three times more potent than PGE1 in preventing histamine-induced convulsions, whereas only TR4161 was active in this test system when the test drugs were administered orally. These observations indicate that TR4161 might be therapeutically useful as a non-irritant prostaglandin bronchoidilator in conditions of airway obstruction.
D000284:Administration, Oral; D000336:Aerosols; D000527:Alprostadil / Q000031:analogs & derivatives*; D000758:Anesthesia; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D001980:Bronchi / Q000187:drug effects*; D001993:Bronchodilator Agents / Q000009:adverse effects; D002415:Cats; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects*
D000336:Aerosols; D001993:Bronchodilator Agents; D011459:Prostaglandins E, Synthetic; C025394:TR4161; D006632:Histamine; D000527:Alprostadil