Naunyn Schmiedebergs Arch Pharmacol. 2009 Dec;380(6):473-7. doi: 10.1007/s00210-009-0462-4. Epub 2009 Nov 11.
Doxazosin and related, quinazoline-based alpha(1)-adrenoceptor antagonists can induce apoptosis in prostate and various other normal, benign, smooth muscle, endothelial and malignant cells. Such apoptosis-inducing effects occur independently of alpha(1)-adrenoceptor antagonism and typically require much high concentrations than those required for receptor occupancy. Several studies have invested efforts towards the elucidation of the molecular mechanisms underlying doxazosin-induced apoptosis. These include various tumor cells, cardiomyocytes, endothelial cells and bladder smooth muscle cells. While the high concentrations of doxazosin required to induce apoptosis challenge the use of this and related drugs for clinical optimization of apoptosis induction, such quinazoline structure may represent chemical starting points to develop more potent apoptosis-inducing agents free of alpha(1)-adrenoceptor antagonistic action and suitable for cancer treatment with minimal and well-tolerated side effects.
多沙唑嗪和相关的喹唑啉类 α1-肾上腺素受体拮抗剂可诱导前列腺和各种其他正常、良性、平滑肌、内皮和恶性细胞凋亡。这种诱导凋亡的作用独立于 α1-肾上腺素受体拮抗作用，通常需要比受体占据所需的浓度高得多。已有多项研究致力于阐明多沙唑嗪诱导凋亡的分子机制。这些研究包括各种肿瘤细胞、心肌细胞、内皮细胞和膀胱平滑肌细胞。虽然诱导凋亡所需的多沙唑嗪高浓度对其和相关药物在诱导凋亡的临床优化中的应用提出了挑战，但这种喹唑啉结构可能代表了开发更有效、无 α1-肾上腺素受体拮抗作用的诱导凋亡剂的化学起点，适用于癌症治疗，副作用小且易于耐受。
