Tejani-Butt S M, Brunswick D J
Life Sci. 1987 Aug 24;41(8):995-1002. doi: 10.1016/0024-3205(87)90688-6.
Although (-)-125I-iodopindolol (IPIN) can be used to label beta-adrenergic receptors in the central nervous system (CNS) in vivo, use of this ligand for receptor imaging studies in humans may be limited due to its relatively poor penetration into the CNS. A series of derivatives related to pindolol was therefore studied in an effort to determine the factors that might influence the penetration and interaction of these compounds with central beta-adrenergic receptors in vivo. Evaluation of the ability of these derivatives to displace the binding of IPIN in the brain upon systemic administration provides an assessment of whether the derivatives penetrate and interact with central beta-adrenergic receptors in vivo. Multiple regression analyses showed that the most important factor which influences the ability of the pindolol derivatives to penetrate into the brain and interact with beta-adrenergic receptors in vivo is the affinity of the derivatives for binding to beta-adrenergic receptors in vitro. Both lipophilicity and the molecular weights of the derivatives are important secondary factors which influence their in vivo potency.
尽管（-）-125I-碘吲哚洛尔（IPIN）可用于在体内标记中枢神经系统（CNS）中的β-肾上腺素能受体，但由于其对CNS的穿透性相对较差，该配体在人体受体成像研究中的应用可能受到限制。因此，研究了一系列与吲哚洛尔相关的衍生物，以确定可能影响这些化合物在体内穿透以及与中枢β-肾上腺素能受体相互作用的因素。评估这些衍生物在全身给药后取代脑中IPIN结合的能力，可评估这些衍生物在体内是否穿透并与中枢β-肾上腺素能受体相互作用。多元回归分析表明，影响吲哚洛尔衍生物在体内穿透大脑并与β-肾上腺素能受体相互作用能力的最重要因素是衍生物在体外与β-肾上腺素能受体结合的亲和力。衍生物的亲脂性和分子量都是影响其体内效力的重要次要因素。
