Имитирующее средство

Один из путей — искать средство, которое имитировало бы постсинаптическое действие ацетилхолина, причем только там, где его недостает. Некоторые предварительные результаты, полученные Р. Харбо из Медицинского центра Дартмута—Хичкока, позволяют думать, что это все же возможно. Другой путь — увеличить выделение ацетилхолина из пресинаптических окончаний, чего можно было бы достичь, создав препарат, избирательно блокирующий ацетилхолиновые рецепторы только на пресннаптических холинэргнческих окончаниях. В отсутствие модулирующего сигнала от этих рецепторов при каждом разряде нейрона его окончание выделяло бы больше ацетилхолина. Можно также пытаться найти ингибитор ацетилхо- линэстеразы, который действовал бы лишь там, где медиатора не хватает; такое вещество продлевало бы действие имеющегося ацетилхолина, так как не происходило бы его расщепления.

Наиболее очевидная стратегия — увеличение синтеза ацетилхолина в оставшихся нервных окончаниях путем снабжения ключевого фермента, ХАТ, большим количеством холина. К счастью, в возбужденных нейронах ХАТ более чувствительна к добавочному холину чем в нейронах, находящихся в состоянии покоя. Холинэргнческие нейроны имеют тенденцию чаше давать разряд в тех областях мозга, где выделение ацетилхолина недостаточно. Можно, таким образом, надеяться, что добавочный холин, полученный пациентом, окажет свое воздействие избирательно — там, где не хватает ацетилхолина; именно такой эффект и требуется.

В моей лаборатории здоровым людям, добровольно участвовавшим в экспериментах, давали холин (или же лецитин, который распадается в организме с образованием холина) в таком количестве, что концентрация холина в крови достигала у них величины, которая, судя по опытам с крысами, достаточна для того, чтобы поднять уровень холина в мозгу, а следовательно, и усилить выделение ацетилхолина из часто возбуждающихся нейронов*. Дж. Гроудон (сотрудник Медицинской школы Гарвардского университета и Массачусетского технологического института) обнаружил, что при этом возрастает уровень холина в спинномозговой жидкости, а значит, добавочный холин действительно достигает головного мозга.





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