Buccafusco J J, Wei J, Kraft K L
Department of Pharmacology Medical College of Georgia, Augusta 30912-2300.
Synapse. 1991 Aug;8(4):301-6. doi: 10.1002/syn.890080408.
Vesamicol (AH5183) inhibits the uptake of acetylcholine into cholinergic neuronal storage vesicles. Earlier in vitro studies have demonstrated that such inhibition can lead to a failure of transmission, particularly in peripheral cholinergic tissues. The present study was designed to determine whether vesamicol could inhibit central cholinergic transmission in conscious freely moving rats. Central (lateral cerebroventricular) injection of 20 micrograms of vesamicol significantly reduced the hypertensive and bradycardic response to subsequent central injection of physostigmine in spontaneously hypertensive rats. Inhibition of the pressor response was greatest when physostigmine was administered 1 hr after vesamicol. Acetylcholine and choline levels were determined in three brain regions derived from rats treated one hr earlier with either vehicle or vesamicol. Acetylcholine levels were found to be unaltered after vesamicol treatment, although choline levels were significantly higher in two brain regions. These results are consistent with the ability of vesamicol to inhibit the function of central cholinergic cardiovascular regulatory neurons. The mechanism for this inhibition is not related to depletion of total brain acetylcholine content but may be due to depletion of a small critical pool of transmitter.
维生米可（AH5183）抑制乙酰胆碱摄取进入胆碱能神经元储存囊泡。早期的体外研究表明，这种抑制作用可导致传递功能障碍，尤其是在外周胆碱能组织中。本研究旨在确定维生米可是否能抑制清醒自由活动大鼠的中枢胆碱能传递。向自发性高血压大鼠侧脑室中央注射20微克维生米可，可显著降低随后向其脑室内中央注射毒扁豆碱所引起的高血压和心动过缓反应。当在注射维生米可1小时后给予毒扁豆碱时，对升压反应的抑制作用最强。对预先分别用赋形剂或维生米可处理1小时的大鼠的三个脑区中的乙酰胆碱和胆碱水平进行了测定。发现维生米可处理后乙酰胆碱水平未改变，尽管在两个脑区中胆碱水平显著升高。这些结果与维生米可抑制中枢胆碱能心血管调节神经元功能的能力是一致的。这种抑制作用的机制与全脑乙酰胆碱含量的耗竭无关，而可能是由于一小部分关键递质池的耗竭所致。
