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Potential therapeutic targets for the treatment of detrusor overactivity.

机译:治疗逼尿肌过度活跃的潜在治疗靶标。

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Current treatments for the overactive detrusor are poorly tolerated and can exert significant adverse effects. Possible targets for the development of new treatments are considered. Potential targets in four locations are examined: detrusor smooth muscle, urothelium, peripheral nerves and the CNS. In the detrusor, the role of various muscarinic receptor subtypes is discussed and beta-adrenoceptor agonists, phosphodiesterase inhibitors and potassium channel openers, all of which inhibit detrusor contractility, are considered for drug development. In the urothelium, a number of substances are released that affect bladder function including ATP, acetylcholine and an inhibitory factor that has yet to be identified. All three systems have the potential to be novel targets for drug development. Other possible therapeutic targets are the mechanisms influencing transmitter release in the bladder, for example, prejunctional 5-hydroxytryptamine (5-HT) 4 receptors. Finally, targets within the CNS and spinal cord are considered, including opioid receptors, 5-HT receptors and alpha-adrenoceptors.
机译:目前对逼尿肌过度活跃症的治疗耐受性差,并且可能产生重大不良影响。考虑开发新疗法的可能目标。检查了四个位置的潜在目标:逼尿肌平滑肌,尿路上皮,周围神经和中枢神经系统。在逼尿肌中,讨论了多种毒蕈碱受体亚型的作用,并考虑了β-肾上腺素受体激动剂,磷酸二酯酶抑制剂和钾通道开放剂,它们均抑制逼尿肌的收缩性,以用于药物开发。在尿道上皮中,释放出许多会影响膀胱功能的物质,包括ATP,乙酰胆碱和尚未确定的抑制因子。所有这三个系统都有可能成为药物开发的新目标。其他可能的治疗靶点是影响膀胱中递质释放的机制,例如结前的5-羟色胺(5-HT)4受体。最后,考虑中枢神经系统和脊髓内的靶标,包括阿片受体,5-HT受体和α-肾上腺素受体。

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