Hara Hideaki, Ichikawa Masaki, Oku Hidehiro, Shimazawa Masamitsu, Araie Makoto
Department of Biofunctional Molecules, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan.
Cardiovasc Drug Rev. 2005 Spring;23(1):43-56. doi: 10.1111/j.1527-3466.2005.tb00156.x.
Bunazosin hydrochloride is a potent and selective alpha1-adrenoceptor antagonist that has been clinically used both as a systemic antihypertensive as well as an ocular hypotensive drug. In a number of studies, we have examined some effects of bunazosin hydrochloride that might indicate its potential as an anti-glaucoma drug. In normal rabbit eyes, topically instilled bunazosin hydrochloride reached the posterior retina by local penetration at concentrations sufficient to attenuate the phenylephrine- or endothelin-1 (ET-1)-induced constriction of retinal arteries. Furthermore, bunazosin hydrochloride improved the impairment of optic nerve head (ONH) blood flow, the prolongation of visual-evoked potentials (VEP) implicit time, the enlargement of the optic disk cup, and the decrease in the number of retinal ganglion cell layer cells induced by repeated injections of ET-1 in rabbits. Topically instilled bunazosin hydrochloride improved the reductions in ONH capillary blood flow and VEP amplitude induced in rabbit eyes by nitric oxide synthase inhibition. In rat primary retinal cultures, bunazosin hydrochloride reduced glutamate-induced neuronal cell death, presumably through a Na+ channel blocking effect. In healthy humans, topically instilled bunazosin hydrochloride reportedly increases blood velocity in the ONH, retina and choroid, without significantly altering either blood pressure or heart rate. These results indicate that bunazosin hydrochloride exerts both an improvement effect within the ocular circulation and a direct neuroprotective effect. Hence, bunazosin hydrochloride may be useful as a therapeutic drug against ischemic retinal diseases (such as glaucoma and retinal vascular occlusive diseases) that are associated with disturbances of the ocular circulation.
盐酸布那唑嗪是一种强效且具有选择性的α1肾上腺素能受体拮抗剂，已在临床上用作全身性抗高血压药物以及降眼压药物。在多项研究中，我们研究了盐酸布那唑嗪的一些作用，这些作用可能表明其作为抗青光眼药物的潜力。在正常兔眼中，局部滴注的盐酸布那唑嗪通过局部渗透到达视网膜后部，其浓度足以减弱去氧肾上腺素或内皮素-1（ET-1）诱导的视网膜动脉收缩。此外，盐酸布那唑嗪改善了重复注射ET-1诱导的兔视神经乳头（ONH）血流受损、视觉诱发电位（VEP）潜伏期延长、视盘杯扩大以及视网膜神经节细胞层细胞数量减少的情况。局部滴注盐酸布那唑嗪改善了一氧化氮合酶抑制诱导的兔眼ONH毛细血管血流减少和VEP振幅降低的情况。在大鼠原代视网膜培养物中，盐酸布那唑嗪可能通过阻断Na+通道减少了谷氨酸诱导的神经元细胞死亡。据报道，在健康人中，局部滴注盐酸布那唑嗪可增加ONH、视网膜和脉络膜中的血流速度，而不会显著改变血压或心率。这些结果表明，盐酸布那唑嗪既对眼循环有改善作用，又有直接的神经保护作用。因此，盐酸布那唑嗪可能作为一种治疗药物，用于治疗与眼循环障碍相关的缺血性视网膜疾病（如青光眼和视网膜血管阻塞性疾病）。
