Abstract |
The effects of 3-dimethylamino 5-(2',6'-dichlorobenzylidene) 6-methyl (4H)-pyridazine ( PC 89) on the biosynthesis of PG I2 and TX A2 using horse aorta and horse platelet microsomes as sources of enzymes and arachidonic acid as substrate, were investigated. PC 89 (1.10(-6) M- 1.10(-3) M) dose-dependently - enhanced the biosynthesis of PG I2: the AD50 was 6.8 X 10(-6) M +/- 1.2 X 10(-9) M, the Vmax did not vary significantly with concentrations: PC 89 increased the affinity of enzyme for substrate - but inhibited TX A2 biosynthesis (ID50 = 3.31 X 10(-3) M +/- 4.8 X 10(-7) M): this inhibiting action was not of competitive type. Owing to this dual activity of preventing TX A2 formation and stimulating PG I2 biosynthesis, PC 89 could be a valuable drug for myocardial ischemia and atherosclerosis therapeutics.
|
Authors | H C Pham, B Lasserre, P Tronche, J Couquelet, V Dossou-Gbete, A L Palhares de Miranda |
Journal | Prostaglandins, leukotrienes, and medicine
(Prostaglandins Leukot Med)
Vol. 19
Issue 1
Pg. 37-49
(Jul 1985)
ISSN: 0262-1746 [Print] Scotland |
PMID | 3929276
(Publication Type: Journal Article)
|
Chemical References |
- Arachidonic Acids
- Pyridazines
- Thromboxanes
- Arachidonic Acid
- Thromboxane A2
- 3-dimethylamino-5-(2',6'-dichlorobenzylidene)-6-methyl(4H)-pyridazine
- Epoprostenol
|
Topics |
- Animals
- Aorta
(metabolism)
- Arachidonic Acid
- Arachidonic Acids
(metabolism)
- Blood Platelets
(metabolism)
- Coronary Disease
(drug therapy)
- Epoprostenol
(biosynthesis)
- Horses
- In Vitro Techniques
- Kinetics
- Microsomes
(metabolism)
- Pyridazines
(pharmacology)
- Thromboxane A2
(biosynthesis)
- Thromboxanes
(biosynthesis)
|