O'Connell A, Earley B, Leonard B E
Pharmacology Department, University College, Galway, Ireland.
Neurochem Int. 1994 Dec;25(6):555-66. doi: 10.1016/0197-0186(94)90154-6.
In this study chronic (39 days) tacrine (3 mg/kg i.p.) treatment significantly improved trimethyltin (8 mg/kg i.p.) induced deficits in spatial navigation. Tacrine also reduced trimethyltin induced hyperactivity and passive avoidance deficits but these effects did not reach statistical significance. The effect of trimethyltin on muscarinic (M1 and M2) receptor sites was determined by means of quantitative autoradiography using [3H]quinuclidinyl benzilate. A selective pattern of M1 and M2 receptor loss was observed mainly affecting the hippocampus and other limbic structures while leaving other brain regions intact. Tacrine successfully prevented the M1 and M2 receptor loss in the CA1 and CA4 hippocampal subfields. The improvement in trimethyltin behavioural toxicity following tacrine treatment may be related to the protective effect of this compound on muscarinic receptor density in the hippocampal formation and lends support to the hypothesis that cholinergic system dysfunction may be primarily responsible for trimethyltin induced deficits in cognitive function.
在本研究中，慢性（39天）给予他克林（腹腔注射3毫克/千克）显著改善了三甲基锡（腹腔注射8毫克/千克）诱导的空间导航缺陷。他克林还减少了三甲基锡诱导的多动和被动回避缺陷，但这些效果未达到统计学显著性。通过使用[3H]喹核醇基苯甲酸酯的定量放射自显影法测定了三甲基锡对毒蕈碱（M1和M2）受体位点的影响。观察到M1和M2受体丢失的选择性模式，主要影响海马体和其他边缘结构，而其他脑区保持完整。他克林成功地预防了CA1和CA4海马亚区的M1和M2受体丢失。他克林治疗后三甲基锡行为毒性的改善可能与该化合物对海马结构中毒蕈碱受体密度的保护作用有关，并支持胆碱能系统功能障碍可能是三甲基锡诱导的认知功能缺陷的主要原因这一假说。
