Adenosine anticonvulsant action

The mechanism of action of carbamazepine appears to be similar to that of phenytoin. Like phenytoin, carbamazepine shows activity against maximal electroshock seizures. Carbamazepine, like phenytoin, blocks sodium channels at therapeutic concentrations and inhibits high-frequency repetitive firing in neurons in culture (Figure 24-4). It also acts presynaptically to decrease synaptic transmission. These effects probably account for the anticonvulsant action of carbamazepine. Binding studies show that carbamazepine interacts with adenosine receptors, but the functional significance of this observation is not known. 

Lee KS, Schubert P, Heinemann U (1984) The anticonvulsive action of adenosine a postsynaptic, dendritic action by a possible endogenous anticonvulsant. Brain Res 321(1) 160—164 Lee KS, Lowenkopf T (1993) Endogenous adenosine delays the onset of hypoxic depolarization in the rat hippocampus in vitro via an action at Al receptors. Brain Res 609(1-2) 313-315 Lee JY, Jhun BS, Oh YT, Lee JH, Choe W, Baik HH, Ha J, Yoon KS, Kim SS, Kang I (2006) Activation of adenosine A3 receptor suppresses lipopolysaccharide-induced TNF-alpha... 

Consistent with the abiUty of vinpocetine to act as an anticonvulsant is its abiUty to inhibit cellular reuptake of adenosine (15) which has been described as the brain s endogenous anticonvulsant because of its abiUty to inhibit calcium influx. Thus the property of vinpocetine to inhibit adenosine reuptake maybe responsible for the neuroprotective actions of the dmg. 

Adenosine and inosine can be transported across cell membranes in either direction, facilitated by a membrane-associated nucleoside transport protein. Concentrative transporters have also been identified. Messenger RNA for a pyrimidine-selective Na+-nucleoside cotransporter (rCNTl) and a purine-selective Na+-nucleoside cotransporter (rCNT2) are found throughout the rat brain. Most degradation of adenosine is intracellular, as evidenced by the fact that inhibitors of adenosine transport, such as dipyridamole, increase interstitial levels of adenosine. Dipyridamole is used clinically to elevate adenosine in coronary arteries and produce coronary vasodilation. In high doses, dipyridamole can accentuate adenosine-receptor-mediated actions in the CNS, resulting in sedation and sleep, anticonvulsant effects, decreased locomotor activity and decreased neuronal activity. 

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