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Cognitive Effects of Three β-Adrenoceptor Acting Drugs in Healthy Volunteers and Patients with Parkinson's Disease.
- Source :
-
Journal of Parkinson's disease [J Parkinsons Dis] 2024; Vol. 14 (6), pp. 1149-1161. - Publication Year :
- 2024
-
Abstract
- Background: Noradrenergic signaling declines in Parkinson's disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that β-acting drugs slow PD progression.<br />Objective: The primary objective was to compare the safety and effects of 3 β-adrenoceptor (β-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of β-AR acting drugs in HVs and PD-patients.<br />Methods: In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and/or clenbuterol (20μg on Day 1, 40μg on Day 2, 80μg on Days 3-7) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests.<br />Results: Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral β2-AR effects were observed with clenbuterol.<br />Conclusions: This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS.
- Subjects :
- Humans
Male
Female
Middle Aged
Aged
Adult
Adrenergic beta-Agonists pharmacology
Adrenergic beta-Agonists administration & dosage
Healthy Volunteers
Parkinson Disease drug therapy
Parkinson Disease metabolism
Clenbuterol pharmacology
Clenbuterol administration & dosage
Clenbuterol adverse effects
Cross-Over Studies
Pindolol pharmacology
Pindolol administration & dosage
Albuterol pharmacology
Albuterol administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1877-718X
- Volume :
- 14
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of Parkinson's disease
- Publication Type :
- Academic Journal
- Accession number :
- 39213090
- Full Text :
- https://doi.org/10.3233/JPD-240039