Representative PET images illustrating distribution of [¹¹C] WAY-100635 in rat brains at baseline and after oral administration of E2110.

<p>PET images were generated by averaging dynamic data at 60-90 min after intravenous radiotracer injection, and were overlaid on the MRI template shown in the far left column. Coronal brain sections shown here were obtained at 1.0 mm (top row), -7.8 mm (middle row) and -12.5 mm (bottom row) from the bregma. ROIs (dotted lines) were defined on the MPFC (top row), DRN (middle row) and cerebellum (CER; bottom row). The radiotracer retention was presented as a percentage of the injected dose per unit tissue volume (%ID/mL).</p

Time course data of rat 5-HT_1A RO in MPFC (●) and DRN (◇), and plasma E2110 concentration (thick dashed line) (A), and plot of RO against plasma E2110 concentration at individual time points (B).

<p>5-HT_1A RO was determined at assigned time points after oral administration of E2110 at a dose of 1 mg/kg. Symbols represent mean ± S.E.M at indicated time points (n = 4/time point). Lines indicate the predicted occupancy versus plasma concentration in MPFC (solid line) and DRN (dashed line).</p

Effects of E2110 on micturition interval in 8-OH-DPAT-infused (A) and SCL (B) rats.

<p>Values are expressed as mean ± S.E.M. of eight rats in 8-OH-DPAT-infused and SCL models; * <i>P</i> < 0.05 versus vehicle (Dunnett’s multiple test).</p

Schematic illustration of a model for description of E2110 PK/PD.

<p>C_p, E2110 concentration in the central compartment; C_e, E2110 concentration in the effect compartment; k_a, absorption rate constant; k_e0, equilibrium rate constant; V₁, central volume of distribution; V₂, peripheral volume of distribution.</p

Relationship between rat 5-HT_1A RO (MPFC: ●, DRN: ◇) and E2110 plasma concentration.

<p>5-HT_1A RO was determined at 4 hours after oral administration of E2110 at a dose ranging from 0.3 to 10 mg/kg. Symbols represent individual data from all dose levels (n = 4/dose level).</p

Effect compartment model estimation of 5-HT_1A RO in DRN after oral administration of E2110 at doses of 0.03, 0.1 and 0.3 mg/kg to female rats.

<p>Solid circle and error bars represent mean RO ± S.E.M measured by PET scans in female rats (n = 3).</p

<i>In vitro</i> inhibition profiles of E2110 and WAY-100635 on 5-HT_1A receptors.

<p>Inhibition of specific [³H] MPPF binding in rat hippocampal membrane homogenates was measured at various concentrations of E2110 (●) and WAY-100635 (○).</p

Chemical structure of E2110.

<p>Chemical structure of E2110.</p