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[Comparative pharmacology of glycerol-1-nitrate and glyceryl trinitrate in various species].

Arzneimittel-Forschung (1986-05-01)
M Leitold, H Laufen, R A Yeates
ABSTRACT

The present studies yield that all 4 metabolites of glyceryl trinitrate (Nitro Mack, GTN) cause the same typical pharmacological effects as the parent substance. Continuous infusion of 4 mg/kg/min of glyceryl 1-nitrate (G-1-N) in the conscious dog results in a drop in blood pressure which is maintained for at least 20 min after stopping the infusion. Under comparable conditions the reduction in blood pressure caused by glyceryl 2-nitrate (G-2-N) (infused at 16 mg/kg/min) decreases by only 3 mmHg. The drop in blood pressure caused by a continuous infusion with GTN (8 micrograms/kg/min) disappeared 10 to 12 min after the end of the infusion. GTN is active in rat, dog and man for 15 to 30 min. Our experiments indicate that after oral administration to the rat or dog glyceryl 1,2-dinitrate (1,2-GDN) and glyceryl 1,3-dinitrate (1,2-GDN) are active for 3 h. Earlier experiments have shown that the administration of high oral doses of 1,2-GDN or 1,3-GDN (280 mg/kg) to the rat increases the time of action to 5-6 h. This is taken as indication that the dinitrates form pharmacologically active metabolites. 1,3-GDN (70 mg/kg p.o.) and 1,2-GDN (140 mg/kg p.o.) exhibited antianginal activity in the rat for 3 or 2 h, respectively. Orally administered GTN is only active for 15 min in the rat or dog. Its pharmacological activity after this time and up to 2-3 h on the rat (280 mg/kg p.o.) and on the dog (4 mg/kg p.o.) is brought about by the dinitrate metabolites (1,2-GDN, 1,3-GDN) and after this time probably only by G-1-N.(ABSTRACT TRUNCATED AT 250 WORDS)

MATERIALS
Product Number
Brand
Product Description

Supelco
1-Mononitroglycerin solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®

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