Disease relevance of Ro 22-4839

• The long-term treatment with Ro 22-4839 prevented the progress of stroke and cerebral edema, although the deteriorated cardiovascular parameters were not prevented by the treatment [1].
• In the video camera system monitoring the constrictory response of feline pial small vessels of the parietal cortex to hypocapnia, Ro 22-4839 was found to reverse vasoconstriction of both pial arteries and veins at the dose of 0.3 mg/kg i.v./min, which did not dilate these vessels under normocapnia [2].

High impact information on Ro 22-4839

• In contrast, Ro 22-4839 hardly inhibited calmodulin-activated Ca2+, Mg2+-ATPase from rat erythrocyte membrane or adenylate cyclase from rat brain [3].
• The inhibition of MLCK induced by Ro 22-4839 was completely overcome by addition of excess calmodulin [3].
• The inhibitory action of Ro 22-4839 on the contractile system of the smooth muscle was demonstrated directly by its inhibition of chicken gizzard MLCK [3].
• Use of hydrophobic fluorescence probes showed that Ro 22-4839 binds to the hydrophobic region of calmodulin like other calmodulin antagonists, trifluoperazine and W-7 [3].
• Selective calmodulin inhibition toward myosin light chain kinase by a new cerebral circulation improver, Ro 22-4839 [3].

Biological context of Ro 22-4839

• Ro 22-4839 was found to potently inhibit MLCK with an IC50 value of 3.1 microM but was unable to inhibit the activity of MLCK rendered Ca2+/calmodulin independent by limited tryptic digestion [3].
• Further, Ro 22-4839 inhibited erythrocyte membrane rupture, platelet aggregation and lipid peroxidation.(ABSTRACT TRUNCATED AT 250 WORDS)[4]
• Ro 22-4839 did not significantly change cerebral oxygen consumption regardless of its increase in cerebral oxygen supply, suggesting that its cerebral vasodilating effect was due to its direct relaxing effect on the vascular smooth muscle [2].

Anatomical context of Ro 22-4839

• The arterial relaxation by Ro 22-4839 was hardly overcome by addition of extra calcium and Ro 22-4839 did not alter calcium channels in the guinea-pig papillary muscle, although the compound inhibited the tension development, confirming its calmodulin antagonistic properties [5].

Associations of Ro 22-4839 with other chemical compounds

• Vasodilating action of a new calmodulin antagonist, 6,7-dimethoxy-1-(3,4-dimethoxybenzyl)-4-([4-(2-methoxyphenyl)- 1-piperazinyl]methyl) isoquinoline (Ro 22-4839), was examined in anesthetized animals [2].

Gene context of Ro 22-4839

• These findings indicate that Ro 22-4839 exerts the spasmolytic effects on cerebral vessels through calmodulin antagonistic properties combined with alpha 1-adrenoceptor blocking action [5].

References