Noronha-Blob L, Lowe V C, Peterson J S, Hanson R C
NOVA Pharmaceutical Corporation, Baltimore, Maryland.
J Pharmacol Exp Ther. 1989 Nov;251(2):586-93.
The anticholinergic, antispasmodic and local anesthetic properties of agents indicated for the treatment of neurogenic bladder disorders were compared with known reference drugs in vitro and in cystometric studies in vivo in the guinea pig. Highly significant correlations (P = .0001) were found among the potencies of drugs to inhibit carbachol-induced isolated guinea pig detrusor muscle contraction in vitro and peak intravesical bladder pressure in vivo in the guinea pig cystometrogram, a test that provides the integrated micturition response in the intact animal. In contrast, there was no significant correlation (P greater than .5) among the potencies of the drugs to depress bladder contractile responses (in vitro and in vivo in the cystometrogram) and their potencies as antispasmodic or local anesthetic agents. Based on these correlations, we suggest that the anticholinergic component of the drugs' action is important in current effective therapies of bladder dysfunction. However, the possibility that other ancillary activities may also contribute to the specific mechanism of action of these agents in the urinary bladder is not ruled out.
在体外以及豚鼠体内膀胱内压测量研究中,将用于治疗神经源性膀胱疾病的药物的抗胆碱能、解痉和局部麻醉特性与已知的参考药物进行了比较。在体外抑制卡巴胆碱诱导的豚鼠离体逼尿肌收缩的药物效力与豚鼠膀胱内压测量图中体内膀胱内压峰值之间发现了高度显著的相关性(P = .0001),该测试可在完整动物中提供综合排尿反应。相比之下,药物抑制膀胱收缩反应的效力(体外和膀胱内压测量图中的体内)与其作为解痉剂或局部麻醉剂的效力之间没有显著相关性(P大于.5)。基于这些相关性,我们认为药物作用的抗胆碱能成分在当前膀胱功能障碍的有效治疗中很重要。然而,并不排除其他辅助活性也可能有助于这些药物在膀胱中作用的具体机制的可能性。