[The blockade of glutaminergic and cholinergic ion channels by adamantane derivatives]

It has been shown that a homologous series of adamantane derivatives of general structure Ad-CH2-N+H2-(CH2)5-N+R3, where Ad, adamantane, R varied from H (hydrogen) to t-Bu (tertiary butyl), blocks the open state of postsynaptic activated channels. In the presence of the drugs studied the decay of evoked cholinergic postsynaptic currents in frog neuromuscular junction could be fitted by two exponentials. However, the rate constants of interaction of blocker with channel did not depend on the R structure and membrane potential. The rate of blockade of glutamatergic postsynaptic currents in insect neuromuscular junction increased as the radicals at nitrogen atom became heavier, but was independent on membrane potential. The drugs studied affected in voltage dependent manner the kinetic properties of single channels (recorded in outside-out patches excised from cultured neurones of embryonic rat brain cortex) induced by NMDA application. Each of these compounds evoked fast flickering of single channels between an open and blocked state. Drugs effectively prevented the convulsions evoked by intraventricular injection of NMDA into mouse brain. The compound IEM-1754 that was the most potent blocker in the experiments on NMDA-activated single channels possessed six times higher anticonvulsant activity than dizocilpine (MK-801).