Abstract
1146
Objectives: An herb medicine PDC949 was developed for antidepression. To investigate the pharmacodynamics, the aim of this study was to evaluate the effect of PDC949 on the binding site of the norepinephrine transporter (NET) with [123I]MIPP by quantitative autoradiography (QARG). Methods: Male Sprague-Dawley rats (350-380 grams) and NET tracer [123I]MIPP were used in this study. Trans-axial 40 μm brain section-mounted slices were used for in vitro autoradiography and incubated in various concentrations of desipramine (selective norepinephrine reuptake inhibitor) or PDC949 for competition assay. For ex vivo autoradiography, PDC949 was orally administered to rats prior to [123I]MIPP i.v. injection (187 MBq). The rats were sacrificed after 80 min radioligand distribution and the brain was cut into 20 um trans-axial sections using a cryostat microtome (CM3050, Leica, Germany). The brain sections were placed on the IP (BAS-SR, FUJI, Japan) in the IP cassette (2040, FUJIFILM, Japan) for 24 hrs. The IP was read by a bio-imaging analyzer (FLA-5000, FUJIFILM, Japan) to acquire the phosphor image. Binding ratios in the anteroventricular thalamic nucleus nucleus (AV), locus coeruleus (LC) and cortex to striatum were calculated. Results: In vitro autoradiography showed a dose-dependent manner both in desipramine and PDC949-treated group. The concentration of desipramine needed to reach the same inhibition was about 100 times less than PDC949. Intense labeling was observed in regions known as the norepinephrine transporter rich sites, such as AV and LC in ex vivo autoradiography. The AV, LC and cortex to striatum (Str) binding ratio in control group were 2.88, 2.37 and 1.84, respectively. The binding ratios of AV/Str and LC/Str in acute and chronic desipramine-treated groups were significant lower than control rat. Chronic PDC949-treated group showed the binding of [123I]MIPP to LC and cortex were reduced. Conclusions: The binding of [123I]MIPP was blocked by both desipramine and PDC949 in a dose-dependent manner as shown in this work. Compared to desipramine, the herb medicine PDC949 showed a mild effect on NET binding. The inhibition site was mainly on the cortex as revealed by ex vivo autoradiography.
- Society of Nuclear Medicine, Inc.