[(18)F]FE-PE2I allowed reliable quantification of DAT, not only in the caudate and putamen but also in the substantia nigra. From the results, we demonstrated the age-related decline in the caudate and putamen as reported in previous studies, and additionally for those in the substantia nigra for the first time.

Background Transdermal antipsychotic patch formulations offer potential benefits, including improved adherence. This study investigated the striatal dopamine D2 receptor occupancy with daily blonanserin transdermal patch application. Methods This open-label, Phase 2 study enrolled 18 Japanese outpatients (20 to <65 years) with schizophrenia (DSM-IV-TR criteria; total Positive and Negative Syndrome Scale [PANSS] score <120 at screening) treated with blonanserin 8 mg or 16 mg tablets. Patients continued tablets for 2-4 weeks at their current dose and were then assigned to once-daily blonanserin patches (10/20/40/60/80 mg daily) for 2-4 weeks based on the oral dose. [ 11C]raclopride PET scanning determined blonanserin striatal dopamine D2 receptor occupancy (primary endpoint). Secondary endpoints included assessment of receptor occupancy by dose, changes in PANSS and CGI-S scores, patient attitudes towards adherence, and patch adhesiveness. Results Of 18 patients who started the blonanserin tablet treatment period, 14 patients completed treatment. Mean D2 receptor occupancy for blonanserin tablets 8 mg/day (59.2%, n=5) and 16 mg/day (66.3%, n=9) was within the values for blonanserin patches: 10 mg/day (33.3%, n=3), 20 mg/day (29.9%, n=2), 40 mg/day (61.2%, n=3), 60 mg/day (59.0%, n=3), and 80 mg/day (69.9%, n=3). Occupancy generally increased with increasing blonanserin dose for both formulations with the half maximal receptor occupancy for tablets and patches associated with doses of 6.9 mg/day and 31.9 mg/day, respectively. Diurnal variability in occupancy was lower during transdermal patch treatment than during tablet treatment. Blonanserin transdermal patches were well tolerated with no major safety concerns. Conclusions Blonanserin patches (40/80 mg/day) have lower diurnal variability in occupancy than blonanserin tablets (8/16 mg/day) and patches at doses of 40 mg/day and 80 mg/day appear to be suitable alternative for blonanserin tablets at doses of 8 mg and 16 mg/day, respectively. Blonanserin patches represent a potential new treatment option for patients with schizophrenia.

AimDysfunction of dopaminergic neurons in the central nervous system is considered to be related to major depressive disorder (MDD). Especially, MDD in geriatric patients is characterized by anhedonia, which is assumed to be associated with reduced dopamine neurotransmission in the reward system. Dopamine transporter (DAT) is considered to reflect the function of the dopamine nerve system. However, previous DAT imaging studies using single photon emission computed tomography or positron emission tomography (PET) have shown inconsistent results. The radioligand [18F]FE‐PE2I for PET enables more precise evaluation of DAT availability. Hence, we aimed to evaluate the DAT availability in geriatric patients with MDD using [18F]FE‐PE2I.MethodsEleven geriatric patients with severe MDD and 27 healthy controls underwent PET with [18F]FE‐PE2I, which has high affinity and selectivity for DAT. Binding potentials (BPND) in the striatum (caudate and putamen), nucleus accumbens (NAc), and substantia nigra were calculated. BPND values were compared between MDD patients and healthy controls.ResultsMDD patients showed significantly lower DAT BPND in the NAc (P = 0.009), and there was a trend of lower BPND in the putamen (P = 0.032) compared to controls.ConclusionWe found low DAT in the NAc and putamen in geriatric patients with severe MDD, which could be related to dysregulation of the reward system.

Modafinil, a wake-promoting drug used to treat narcolepsy, is a dopamine transporter inhibitor and is said to have very low abuse liability; this, however, is still up for debate. We conducted a dopamine transporter (DAT) occupancy study with modafinil (200 or 300 mg) in ten healthy volunteers using positron emission tomography (PET) with [¹⁸F]FE-PE2I, a new PET radioligand with high affinity and selectivity for the dopamine transporter, to characterize its relation to abuse liability. Mean striatal DAT occupancies were 51.4% at 200 mg and 56.9% at 300 mg. There was a significant correlation between occupancy and plasma concentration, indicating dose dependency of DAT inhibition by modafinil in the striatum, and especially in the nucleus accumbens. This study showed that DAT occupancy by modafinil was close to that of methylphenidate, indicating that modafinil may be near the same level as methylphenidate in relation to abuse liability in terms of dopaminergic transmission.

BackgroundBlockade of D3 receptor, a member of the dopamine D2-like receptor family, has been suggested as a possible medication for schizophrenia. Blonanserin has high affinity in vitro for D3 as well as D2 receptors. We investigated whether a single dose of 12 mg blonanserin, which was within the daily clinical dose range (i.e., 8–24 mg) for the treatment of schizophrenia, occupies D3 as well as D2 receptors in healthy subjects.MethodsSix healthy males (mean 35.7±7.6 years) received 2 positron emission tomography scans, the first prior to taking blonanserin, and the second 2 hours after the administration of a single dose of 12 mg blonanserin. Dopamine receptor occupancies by blonanserin were evaluated by [11C]-(+)-PHNO.ResultsOccupancy of each region by 12 mg blonanserin was: caudate (range 64.3%–81.5%; mean±SD, 74.3±5.6%), putamen (range 60.4%–84.3%; mean±SD, 73.3%±8.2%), ventral striatum (range 40.1%–88.2%; mean±SD, 60.8%±17.1%), globus pallidus (range 65.8%–87.6%; mean±SD, 75.7%±8.6%), and substantia nigra (range 56.0%–88.7%; mean±SD, 72.4%±11.0%). Correlation analysis between plasma concentration of blonanserin and receptor occupancy in D2-rich (caudate and putamen) and D3-rich (globus pallidus and substantia nigra) regions showed that EC50 for D2-rich region was 0.39 ng/mL (r=0.43) and EC50 for D3-rich region was 0.40 ng/mL (r=0.79).ConclusionsA single dose of 12 mg blonanserin occupied D3 receptor to the same degree as D2 receptor in vivo. Our results were consistent with previous studies that reported that some of the pharmacological effect of blonanserin is mediated via D3 receptor antagonism.