Iptakalim是一种ATP敏感性钾通道开放剂,以及含α4β2的烟碱乙酰胆碱受体(nAChR)拮抗剂。用埃他卡姆预处理可减少尼古丁诱导的多巴胺(DA)和伏隔核中的谷氨酸释放。这种神经药理学特征表明,埃他卡林可能可用于治疗尼古丁依赖。因此,我们研究了依他卡林在两种临床前模型中的作用.首先,通过在包括混合尼古丁(0.4mg/kg,SC)和盐水会议。蔗糖仅在尼古丁疗程中以独立于反应的方式间歇性出现。在中间的测试日,大鼠用伊他卡林预处理(10、30、60mg/kg,IP)。结果表明,依他卡林以剂量依赖性方式减弱了由尼古丁刺激控制的尼古丁诱发反应。在另一项研究中,通过训练大鼠杠杆按压以自我给予尼古丁(0.01mg/kg/输注)[校正剂量误差],研究了依他卡林对尼古丁增强作用的影响.结果表明,用伊他卡林(1、3、6mg/kg,IV)尼古丁摄入量减少(即不太活跃的杠杆响应)。两种行为效应都不是由于伊塔卡林的非特异性运动效应,也不具有伊他卡林抑制DA转运蛋白(DAT)或5-羟色胺转运蛋白(SERT)功能的能力。一起,这些发现支持了依他卡林可能是增加戒烟的有效药物疗法的观点,并且更好地理解其作用可能有助于药物开发.
Iptakalim is an ATP-sensitive potassium channel opener, as well as an α4β2-containing nicotinic acetylcholine receptor (nAChR) antagonist. Pretreatment with iptakalim diminishes nicotine-induced dopamine (DA) and glutamate release in the nucleus accumbens. This neuropharmacological profile suggests that iptakalim may be useful for treatment of nicotine dependence. Thus, we examined the effects of iptakalim in two preclinical models. First, the impact of iptakalim on the interoceptive stimulus effect of nicotine was evaluated by training rats in a discriminated goal-tracking task that included intermixed nicotine (0.4 mg/kg, SC) and saline sessions. Sucrose was intermittently presented in a response-independent manner only on nicotine sessions. On intervening test days, rats were pretreated with iptakalim (10, 30, 60 mg/kg, IP). Results revealed that iptakalim attenuated nicotine-evoked responding controlled by the nicotine stimulus in a dose-dependent manner. In a separate study, the impact of iptakalim on the reinforcing effects of nicotine was investigated by training rats to lever-press to self-administer nicotine (0.01 mg/kg/infusion) [Dosage error corrected]. Results revealed that pretreatment with iptakalim (1, 3, 6 mg/kg, IV) decreased nicotine intake (i.e., less active lever responding). Neither behavioral effect was due to a non-specific motor effect of iptakalim, nor to an ability of iptakalim to inhibit DA transporter (DAT) or serotonin transporter (SERT) function. Together, these finding support the notion that iptakalim may be an effective pharmacotherapy for increasing smoking cessation and a better understanding of its action could contribute to medication development.