Effects on cerebral blood flow after single doses of the β agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease.

Aims: Cerebral hypometabolism occurs years prior to a diagnosis of neurodegenerative diseases and coincides with reduced cerebral perfusion and declining noradrenergic transmission from the locus coeruleus. In pre-clinical models, β-adrenoceptor (β-AR) agonists increase cerebrocortical glucose metabolism, and may have therapeutic potential for neurodegenerative diseases. This study investigated the safety and effects on regional cerebral blood flow (rCBF) of the oral, brain-penetrant β-AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD).

SDI-118, a novel procognitive SV2A modulator: First-in-human randomized controlled trial including PET/fMRI assessment of target engagement.

Current treatments for progressive neurodegenerative disorders characterized by cognitive impairment either have limited efficacy or are lacking altogether. SDI-118 is a small molecule which modulates the activity of synaptic vesicle glycoprotein 2A (SV2A) in the brain and shows cognitive enhancing effects in a range of animal models of cognitive deficit. This first-in-human study evaluated safety, tolerability, and pharmacokinetics/pharmacodynamics of SDI-118 in single ascending oral doses up to 80 mg administered to 32 healthy male subjects.

Doppler ultrasound to assess the pharmacodynamic effects of splanchnic vasoactive compounds.

Aims: In search of noninvasive biomarkers to assess the pharmacodynamic effects of portal pressure-lowering drugs, the reproducibility of flow measurements in the superior mesenteric artery was evaluated using Doppler ultrasound.

Methods: A reproducibility study was conducted in 15 healthy male volunteers (18-50 y). Eight ultrasound measurements were performed for each subject: 2 observers each conducted 2 measurements during 2 separate visits.