Effects Of HA1077 Research Articles

The effects of HA1077, a novel protein kinase inhibitor, on reductions of cerebral blood flow and glucose metabolism following acute and/or chronic bilateral carotid artery ligation in Wistar rats

The effects of HA1077, a novel protein kinase inhibitor on local cerebral blood flow (LCBF) 2.5 h (acute) after permanent bilateral carotid artery ligation (BCAL) and on LCBF and local cerebral glucose utilisation (LCGU) one week (chronic) after BCAL were studied in conscious Wistar rats. Use was made of quantitative autoradiographic 14C-iodoantipyrine and the 14C-2-deoxyglucose techniques and 24 anatomically discrete regions of the brain. HA1077 (1 or 3 mg/kg) or saline was infused i.v. over a 30 min period. HA1077 significantly increased LCBF after acute BCAL in one of the 23 decreased regions in rats given 1 mg/kg, and in 14 of 23 decreased regions in rats given 3 mg/kg, compared to findings in the saline-treated group. Significant increases in LCBF and LCGU after chronic BCAL were noted in seven of the 13 decreased regions and in four of the 11 decreased regions in rats given 3 mg/kg, as compared to observations in the corresponding saline-treated group, respectively. The LCBF and LCGU reductions in forebrain regions with global ischaemia after acute and/or chronic BCAL were overcome by HA1077. These results suggest that HA1077 may be considered for treatment of subjects with acute and chronic cerebral ischaemia, with impairment in cerebral circulation and/or glucose metabolism.

P-482 - Effects of HA1077 (fasudil), a novel calciumantagonistic agent, on cerebral anoxia in experimental mice

P-482 - Effects of HA1077 (fasudil), a novel calciumantagonistic agent, on cerebral anoxia in experimental mice

P-481 - Effects of HA1077 (fasudil) on canine cerebral artery strips and regional cerebral blood flow in dogs

P-481 - Effects of HA1077 (fasudil) on canine cerebral artery strips and regional cerebral blood flow in dogs

O-166 - The effects of HA1077 on the experimental subarachnoid hemorrhage in dogs

O-166 - The effects of HA1077 on the experimental subarachnoid hemorrhage in dogs

Effects of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brainIn Vivo

The effect of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain was investigated in vivo. After administration of HA1077, at doses of 0.1, 0.3, and 3 mg/kg, 5-hydroxyindoleacetic acid (5-HIAA) levels increased in most regions except midbrain. In the striatum, parallel increases of both serotonin (5-HT) and 5-HIAA levels were observed at 0.3 mg/kg, but only the 5-HT level increased at 0.1 mg/kg. These results suggest that HA1077 may activate the turnover or synthesis of 5-HT. After administration of HA1077 at 0.3, 1, and 3 mg/kg, the dopamine (DA) level was increased in the striatum, but 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid levels were unchanged. After HA1077 administration at 1 mg/kg, both DA and DOPAC levels increased in the hypothalamus and only DA level increased in the cerebral cortex. By contrast, DOPAC level decreased in the midbrain after HA1077 treatment at 0.1 and 0.3 mg/kg, and in the brainstem at 0.1 and 10 mg/kg. The ratio of [3H]-N-methylspiperone accumulation relative to that in the cerebellum did not change after HA1077 treatment at any of the doses employed. Thus, the effects of HA1077 on neurotransmitter metabolism are complex and vary depending on the dosage and sites of the brain. Although the dose-dependent effects of HA1077 on neurotransmitter metabolism are similar to those of calcium entry blockers, HA1077 can facilitate DA synthesis in the hypothalamus and striatum, unlike the calcium entry blockers.

The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs

We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p less than 0.05) and blood velocity (48% of control, p less than 0.05) with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1-0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH.

P-052 - Effects of HA1077 (fasudil) on delayed neuronal death in Mongolian gerbil.

P-052 - Effects of HA1077 (fasudil) on delayed neuronal death in Mongolian gerbil.

P-178 - Effects of HA1077 on cytosolic Ca++ level and contraction in vascular smooth muscle.

P-178 - Effects of HA1077 on cytosolic Ca++ level and contraction in vascular smooth muscle.

O-062 - Effects of HA1077 on myosin light chain phosphorylation in cultured smooth muscle cells

O-062 - Effects of HA1077 on myosin light chain phosphorylation in cultured smooth muscle cells

O-061 - Effects of HA1077 on tension development and myosin light chain phosphorylation in smooth muscle

O-061 - Effects of HA1077 on tension development and myosin light chain phosphorylation in smooth muscle

O-271 - Effects of HA1077 on delayed cerebral vasospasm in dogs

O-271 - Effects of HA1077 on delayed cerebral vasospasm in dogs