FR144420, a novel, slow, nitric oxide-releasing agent
| Autor: | Shigetaka Nishino, Yasuhiro Kita, Kazumi Ohkubo, Masayuki Kato, Keizo Yoshida, Mitsuko Ohno, Yoshimi Hirasawa, Yoshiki Katayama |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Male
Stereochemistry Muscle Relaxation Vasodilator Agents Metabolite Administration Oral Blood Pressure In Vitro Techniques Pharmacology Nitric Oxide Muscle Smooth Vascular Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Drug Stability Oral administration In vivo Animals Nitrite Incubation Antihypertensive Agents Aorta EC50 Analysis of Variance Nicotinic Acids Stereoisomerism Nitro Compounds Rats Disease Models Animal Muscle relaxation chemistry Hypertension Injections Intravenous Muscle Contraction |
| Zdroj: | European Journal of Pharmacology. 275:125-130 |
| ISSN: | 0014-2999 |
| Popis: | We report that (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409) decomposes and releases nitric oxide (NO) spontaneously in solution. (+/-)-N-[(E)-4-Ethyl-3-[(Z)-hydroxyimino]-5-nitro-3-hexen-1- yl]-3- pyridinecarboxamide (FR144420) was synthesized with the aim of discovering a compound with longer duration of effects in vivo, compared with FK409. FR144420, like FK409, released NO spontaneously in solution, but the amount of NO released from FR144420 during a 5-min incubation was half the amount from FK409. In addition, FR144420 spontaneously decomposed and generated nitrite, which is an oxidative metabolite of NO, at half the rate of FK409. In a vasorelaxant study with isolated rat aorta, FR144420 had a weaker potency than FK409 (EC50 = 54 and 8.1 nM, respectively). In in vivo studies, FR144420 decreased mean blood pressure immediately after intravenous and oral administration to conscious rats. The maximum hypotensive effects of FR144420 were less than those of FK409. However, the durations of FR144420-induced (i.v. and p.o.) hypotensive effects were longer than those of FK409-induced effects. In conclusion, FR144420 is more stable and releases NO more slowly in solution than does FK409. In in vivo experiments, FR144420 showed a longer duration of effects than FK409. FR144420 may be very useful for investigating the in vivo actions of NO. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect