Flagmeyer I, Gebert I, van der Staay F J
Troponwerke, Institute for Neurobiology, Department of Gerontopharmacology, Cologne, Germany.
Arzneimittelforschung. 1995 Apr;45(4):456-9.
The putative cognition enhancer linopirdine (3,3-bis(4-pyrindinylmethyl)-1-phenylindolin-2-one, CAS 105431-72-9) is supposed to act by enhancing the release of neurotransmitters, especially acetylcholine. The present study assessed the effects of a single administration of this compound on the central nervous system in eight different rat and mouse models (CNS general pharmacology). In each test performed, linopirdine was administered subcutaneously in doses of 3, 10, and 30 mg/kg. The compound did not affect traction ability and nociceptive responsiveness nor did it induce catalepsy. Linopirdine impaired motor coordination in the balance rod test. The compound showed a distinct proconvulsive action in the pentylenetetrazole threshold dose test and induced in the highest dose tested (30 mg/kg) lethal seizures in some mice. It increased the duration of hexobarbital-induced anaesthesia in mice. Rats treated with linopirdine showed ptosis, salivation, slight sedation, paw beating and slight hypothermia. These results support the hypothesis that linopirdine acts by elevating the release of different neurotransmitters such as acetylcholine and dopamine. The compound has a low potential to produce side effects at pharmacodynamic active doses.
假定的认知增强剂利诺吡啶（3,3 - 双（4 - 吡啶基甲基）-1 - 苯基吲哚啉 - 2 - 酮，化学物质登记号105431 - 72 - 9）被认为是通过增强神经递质尤其是乙酰胆碱的释放来发挥作用。本研究评估了单次给予该化合物对八种不同大鼠和小鼠模型中枢神经系统的影响（中枢神经系统一般药理学）。在进行的每项试验中，利诺吡啶以3、10和30mg/kg的剂量皮下给药。该化合物不影响牵引能力和伤害性反应，也不诱导僵住症。利诺吡啶在平衡杆试验中损害运动协调性。在戊四氮阈剂量试验中，该化合物表现出明显的惊厥作用，并且在最高测试剂量（30mg/kg）时，一些小鼠出现致死性惊厥。它延长了小鼠中巴比妥诱导的麻醉持续时间。用利诺吡啶治疗的大鼠出现上睑下垂、流涎、轻度镇静、爪击和轻度体温过低。这些结果支持了利诺吡啶通过提高乙酰胆碱和多巴胺等不同神经递质的释放来发挥作用的假说。该化合物在药效学活性剂量下产生副作用的可能性较低。
