Chiou C Y, Chu C J, Liddell N E
Arch Int Pharmacodyn Ther. 1978 Sep;235(1):35-42.
The results of glioma chemotherapy obtained so far have been rather disappointing. New attempts have been made to kill glioma cells with autonomic drugs. Experiments were done with rat C-6 glioma cells in the cell culture. Among all cholinergic blockers tested, only the irreversible cholinergic blockers such as bromoacetylcholine (BrACh), iodoacetylcholine and alphabungarotoxin were effective to inhibit glioma cells (with 50% cytolytic doses of 6.7 x 10(-6)M, 3.0 x 10(-6)M and 7.4 x 10(-5)M respectively). It is interesting to note that the hydrolytic product of BrACh, bromoacetate, was as potent as BrACh to inhibit glioma cells. Most of the adrenergic blockers, both reversible and irreversible ones, showed no cytolytic activity on glioma cells with concentrations up to 1.0 x 10(-4)M except phentolamine and propranolol which showed weak cytolytic activities. It is interesting to note, on the other hand, that 6-hydroxydopamine (an adrenergic neuron degenerating agent) and 5,6-dihydroxytryptamine (a serotonergic neuron degenerating agent) also showed mild cytolytic effects on glioma cells with 50% cytolytic doses of 5.0 x 10(-5)M and 5.3 x 10(-5)M, respectively.
目前为止,胶质瘤化疗的结果相当令人失望。人们已经尝试使用自主神经药物来杀死胶质瘤细胞。在细胞培养中用大鼠C-6胶质瘤细胞进行了实验。在所有测试的胆碱能阻滞剂中,只有不可逆的胆碱能阻滞剂,如溴乙酰胆碱(BrACh)、碘乙酰胆碱和α-银环蛇毒素,对抑制胶质瘤细胞有效(50%细胞溶解剂量分别为6.7×10⁻⁶M、3.0×10⁻⁶M和7.4×10⁻⁵M)。有趣的是,BrACh的水解产物溴乙酸酯与BrACh抑制胶质瘤细胞的效力相同。大多数肾上腺素能阻滞剂,无论是可逆的还是不可逆的,在浓度高达1.0×10⁻⁴M时对胶质瘤细胞均无细胞溶解活性,但酚妥拉明和普萘洛尔表现出较弱的细胞溶解活性。另一方面,有趣的是,6-羟基多巴胺(一种肾上腺素能神经元变性剂)和5,6-二羟基色胺(一种血清素能神经元变性剂)对胶质瘤细胞也表现出轻度的细胞溶解作用,50%细胞溶解剂量分别为5.0×10⁻⁵M和5.3×10⁻⁵M。