Pharmacological comparison of the stereoisomers of glyceryl-1-nitrate.
The enantiomers of glyceryl-1-nitrate, a metabolite of glyceryl trinitrate, were pharmacologically characterized in vitro and in animals. In the Langendorff heart (l) G-1-N was double as potent as (d) G-1-N with respect to the enhancement of coronary flow. The two enantiomers showed almost the same dose-response curves in rabbit aortic strips contracted with phenylephrine. In the same model there were no enantiospecific differences in the development of cross-tolerance to glyceryl-trinitrate. In anaesthetized rabbits, intravenous (l) G-1-N reduced the blood pressure slightly more than (d) G-1-N, while in the conscious dog the blood pressure lowering effect of (d) G-1-N was greater and had a much longer duration (4-6 versus 2 h) than that of (l)G-1-N. The differences in dogs are probably explained by enantiospecific pharmacokinetics: (d) G-1-N had higher plasma levels and showed a longer half-life of elimination than (l) G-1-N (more than 5 h versus 2.7 h). Both enantiomers enhanced the rate of survival after acute coronary ligature in rats with a tendency to higher long-term survival rates after the (d) form.
Department of Pharmacology, Pfizer/Mack R&D, Illertissen, Fed. Rep. of Germany.
T
T
Zimmermann
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M
Leitold
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H
Laufen
K D
KD
Riedel
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P
Stoss
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002682:Chinchilla; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D006168:Guinea Pigs; D006207:Half-Life; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D005996:Nitroglycerin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
C049454:glycerol-1-nitrate; D005996:Nitroglycerin