PT  - JOURNAL ARTICLE
AU  - Y Kita
AU  - Y Hirasawa
AU  - S Fukuyama
AU  - K Ohkubo
AU  - Y Kato
AU  - H Takamatsu
AU  - M Ohno
AU  - S Nishino
AU  - M Kato
AU  - J Seki
TI  - Oral biological activities of spontaneous nitric oxide releasers are accounted for by their nitric oxide-releasing rates and oral absorption manners.
DP  - 1996 Feb 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 421--425
VI  - 276
IP  - 2
4099  - http://jpet.aspetjournals.org/content/276/2/421.short
4100  - http://jpet.aspetjournals.org/content/276/2/421.full
SO  - J Pharmacol Exp Ther1996 Feb 01; 276
AB  - We examined whether p.o. biological activities of (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409), a spontaneous nitric oxide (NO) releaser, and the derivatives, i.e., (+/-)-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexenyl]-3 - pyridinecarboxamide (FR144420) and (+/-)-N-[(E)-4-ethyl-3-[(Z)-hydroxyimino]-6-methyl-5- nitro-3-heptenyl]-3-pyridinecarboxamide (FR146801), could be accounted for by their NO-releasing rates and p.o. absorption manners. These compounds spontaneously released NO with the rates in the rank order of FK409 > FR144420 > FR146801. Total contribution of these drugs as NO donors in vivo was almost the same from the determination of urinary nitrite/nitrate (NOx) levels after p.o. administration of the compounds at 10 mg/kg to rats. Plasma NOx level after p.o. administration of FK409 at 10 mg/kg to rats reached maximal level at 120 min, and decreased gradually. On the other hand, plasma NOx levels time-dependently increased during 360 min after p.o. administration of FR144420 and FR146801 at the same dose. FK409 and FR144420 showed hypotensive effects immediately after p.o. administration at 10 mg/kg to rats, and the maximum response of FR144420 was less and the duration of the effect was longer than those of FK409, respectively. On the other hand, FR146801, which is most stable in solution, did not show any significant hypotensive effect during 240 min after p.o. administration at the same dose. In conclusion, the response and the duration of biological activity after p.o. administration of three spontaneous NO releasers can be closely accounted for by their NO-releasing rates and p.o. absorption manners.