Can a Positive Allosteric Modulation of GABAergic Receptors Improve Motor Symptoms in Patients with Parkinson’s Disease? The Potential Role of Zolpidem in the Treatment of Parkinson’s Disease

Figure 1

Schematic representations of the activity of the cortical-basal ganglia loops, showing the direct (D) and indirect (I) circuits in normal subjects (a), patients with Parkinson’s disease/Parkinsonism (b), and patients with Parkinson’s disease treated with zolpidem (c). In PD [18], zolpidem may induce, through receptors containing the α1 subunit, a selective inhibition of the GPi and the SNr (the two main inhibitory GABAergic output structures of the basal ganglia), which are overactive in PD (b) and show binding sites for zolpidem (c). The inhibition of the GPi and the SNr directly induced by zolpidem may result in an increased activity of some motor cortical areas (such as supplementary motor area), which may underlie the possible improvement of Parkinsonian motor symptoms which can be observed after the administration of zolpidem. Although binding sites for zolpidem in the STN are not displayed in (c), the STN was found to have binding sites for zolpidem [36] and might be reasonably considered an additional target for zolpidem in PD patients. In PD, zolpidem might inhibit the STN as well, giving rise to decreased excitatory inputs from the STN to the GPi and SNr, resulting in a further mechanism leading to a decreased activity of the GPi and SNr, indirectly induced by zolpidem through its inhibition of the STN. White arrows = excitatory connections; black arrows = inhibitory connections.

(a) Normal

(b) Parkinson’s disease

(c) Parkinson’s disease + zolpidem