<i>In vitro</i> autoradiography (ARG) using [³H]TAK-063 in sagittal rat brain sections.

<p>The chemical structure of [³H]TAK-063 (A). Sections adjacent to those used for <i>in vitro</i> ARG of [³H]TAK-063, were stained with hematoxylin and eosin (B). The autoradiogram shows the high accumulation of [³H]TAK-063 in the caudate putamen (CPu; white arrow), nucleus accumbens (NAc; black arrow), globus pallidus (GP; white arrow head), substantia nigra (SN; black arrow head), and striatonigral projection (gray arrow; C). <i>In vitro</i> ARGs in the presence of an excess amount of MP-10 (D) or TAK-063 (E) were performed with adjacent sections. Radioactivity levels in several brain regions were represented as photostimulated luminescence (PSL) values in the presence or absence of an excess amount of MP-10 or TAK-063 (F). Statistical analyses were performed using Dunnett's test (*<i>P</i> ≤ 0.05, **<i>P</i> ≤ 0.01 vs total binding, n = 3). Fcx, frontal cortex; Thal, thalamus; Bs, brainstem; Hipp, hippocampus; Cb, cerebellum.</p

<i>In vitro</i> autoradiography (ARG) using [³H]TAK-063 in mouse brain sections.

<p>[³H]TAK-063 selectively accumulated in the caudate putamen (CPu; black arrow) and nucleus accumbens (NAc; white arrow) of wild-type (WT) mouse brain sections (A). The selective accumulation of [³H]TAK-063 in these areas did not occur in <i>Pde10a</i>-KO mouse brain sections (B). Radioactivity levels in the CPu of brain sections in the presence and absence of an excess amount of MP-10 are represented as a percent of total binding of WT mice (C). Data are represented as mean ± SEM.</p

Percent inhibition of enzymes by TAK-063 at 10 μM.

<p>EGF, epidermal growth factor; HMG CoA, 3-hydroxy-3-methyl-glutaryl coenzyme A. Negative value of percent inhibition indicates activation of enzyme activity.</p><p>Percent inhibition of enzymes by TAK-063 at 10 μM.</p

Concentration of T-773 in the rat brain and displacement by TAK-063.

<p>The data (ng/g tissue) are represented as mean (n = 2 at 0.3 mg/kg) or mean ± SEM (n = 3).</p><p>Concentration of T-773 in the rat brain and displacement by TAK-063.</p

<i>In vivo</i> ARG of [¹⁴C]TAK-063 in rats.

<p>The chemical structure of [¹⁴C]TAK-063 (A). The asterisk denotes the labeled position. Autoradiograms of head sections were obtained from male rats 6 h after single oral administration of [¹⁴C]TAK-063. The autoradiograms of 40 μm sagittal sections between 2.1 to 2.4 mm lateral to midline were taken (B). The locations for each coronal section relative to the bregma were 1.7 to 1.2 mm (C), 0.48 to −0.26 mm (D), −0.4 to −0.8 mm (E), −2.8 to −3.1 mm (F), −6.0 to −6.3 mm (G), and −12.7 to −12.8 mm (H). Acc, nucleus accumbens; Cb, cerebellum; Cpu, caudate putamen; Ctx, cortex; Fcx, frontal cortex; GP, globus pallidus; Hipp, hippocampus; MO, medulla oblongata; OT, olfactory tubercle; SN, substantia nigra; Thal, thalamus; VP, ventral pallidum.</p

Percent inhibition of receptors by TAK-063 at 10 μM.

<p>AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; NMDA, N-methyl-D-aspartic acid. Negative value of percent inhibition indicates stimulation of receptor activity.</p><p>Percent inhibition of receptors by TAK-063 at 10 μM.</p

Saturation binding analysis using [³H]TAK-063 in rat brain coronal sections.

<p>A saturation binding assay was performed with a range of concentrations of [³H]TAK-063. Regions of interest (ROIs) were the bilateral caudate putamen (CPu; arrows) and nucleus accumbens (NAc) shell (arrowheads) in the autoradiograms (A). Total and non-specific binding in each ROI was represented as PSL values (/mm²), and saturation binding curves from the CPu (B) and NAc shell (C) were analyzed by nonlinear regression. K_d values in the CPu and NAc shell were estimated at 7.2 ± 1.2 nM and 2.6 ± 0.5 nM, respectively. All data were represented as mean ± SEM.</p