Although there are various models of neurochemical disturbance underlying seizure genesis and also various models proposed to underlie PD, in both conditions aetiological disruptions of the GABA system have been proposed.
It is well established that GABA exerts an inhibitory control on neuronal excitability by its rapid action on Cl~ channels. The mechanisms of several antiepilep-tic drugs, such as phenobarbitone, vigabatrin and benzodiazepines, involve enhancing GABAergic activity in various ways.
As yet, no specific defect in GABA functioning has been identified in patients with PD. However, GABA is indirectly implicated in PD through benzodiazepines. Benzodiazepine receptor agonists produce neuronal inhibition via benzodiazepine receptor modulation of GABAa receptor mechanisms, leading to, amongst other effects, anxiolysis, muscle relaxation and sedation. Benzodiazepine antagonists occupy the benzodiazepine receptor site without producing pharmacological effects, while inverse agonists, such as beta-carboline, are anxiogenic and procon-vulsant (Katz et al., 1993). Clinical data show that high potency benzodiazepine agonists, such as alprazolam and clonazepam, have marked antipanic effects. Moreover, other studies have suggested subsensitivity of benzodiazepine receptors in these patients (Eison, 1990). Possibly in relation to this, flumazenil, a benzodi-azepine antagonist, has been reported to be panicogenic in patients with PD but not in healthy controls.
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