Effect of Carbidopa Dose on Levodopa Pharmacokinetics With and Without Catechol-O-Methyltransferase Inhibition in Healthy Subjects.

Background And Objectives: The treatment of Parkinson's disease (PD) is still symptomatic since disease-modifying treatments for PD are not available. Oral levodopa is the gold standard for the treatment of PD motor symptoms. However, incomplete and fluctuating plasma exposure of levodopa leads to suboptimal treatment of the symptoms.

Application of the PET ligand [C]ORM-13070 to examine receptor occupancy by the α-adrenoceptor antagonist ORM-12741: translational validation of target engagement in rat and human brain.

Background: Availability of the α-adrenoceptor (α-AR) positron emission tomography (PET) tracer, [C]ORM-13070, and the α-AR antagonist ORM-12741 allows probing of the roles of this G-protein coupled receptor subtype in brain function, both in healthy humans and in patients with various brain disorders. This translational study employed [C]ORM-13070 autoradiography and PET to determine α-AR occupancy by ORM-12741 in rat and human brain, respectively.

Results: ORM-12741 has high affinity (K: 0.

Tolerability of ORM-12741 and effects on episodic memory in patients with Alzheimer's disease.

Introduction: ORM-12741 is a novel selective antagonist of alpha-2C adrenoceptors. This trial evaluated the safety and efficacy of ORM-12741 in patients with Alzheimer's disease (AD).

Methods: A randomized, double-blind, placebo-controlled, exploratory phase 2a trial was conducted in 100 subjects with AD and neuropsychiatric symptoms.

Sensitivity of [(11)C]ORM-13070 to increased extracellular noradrenaline in the CNS - a PET study in human subjects.

Rationale: No validated methods have been available for studying brain noradrenergic neurotransmission in vivo in humans. Positron emission tomography (PET) radiotracers are widely used in clinical drug development targeted to brain receptors and can also in some cases be employed to monitor extracellular (synaptic) neurotransmitter concentrations.

Objectives: The objective of this study is to test the sensitivity of [(11)C]ORM-13070 uptake to increased concentrations of extracellular (synaptic) noradrenaline in the human brain.