11-Deoxy-11 alpha,12 alpha-methanoprostaglandin E2, a potent, short-acting bronchodilator.
11-Deoxy-11 alpha,12 alpha-methanoprostaglandin E2 (1b) and the corresponding methyl ester 7a were highly potent, but short acting, bronchodilators both by the intravenous (80 and 10 times PGE2, respectively) and aerosol (2 and approximately 1 times PGE2) routes, as measured by the Konzett-Rössler assay. The 11 beta,12 beta-methano compound 15a was two orders of magnitude less active than 7a. In rhesus monkeys anesthetized by aerosol administration, 1b was 10-50% as potent as, and had a duration of action similar to, PGE1 in the inhibition of methacholine-induced increases in airway resistance. At doses effective in preventing the methacholine response, 1b increased the heart rate (less than or equal to 30%) and precipitated mild upper airway irritation.
R
R
Davis
G L
GL
Garay
A
A
Guzman
J M
JM
Muchowski
W H
WH
Rooks
A J
AJ
Tomolonis
E
E
Velarde
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D015232:Dinoprostone / Q000031:analogs & derivatives*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006633:Histamine Antagonists; D008253:Macaca mulatta; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology
D000336:Aerosols; D001993:Bronchodilator Agents; D006633:Histamine Antagonists; D008688:Methacholine Compounds; D011459:Prostaglandins E, Synthetic; C048778:11-deoxy-11,12-methanoprostaglandin E2; D006632:Histamine; D015232:Dinoprostone