Objective: This study aimed to assess the effects of β-agonists on central nervous system (CNS) functioning in healthy volunteers and patients with Parkinson’s disease.
Background: Neurodegeneration in the locus coeruleus (LC) causing loss of noradrenergic neurons occurs early in Parkinson’s disease (PD)[1] and may play an important role in the manifestation of non-motor symptoms[2]. Noradrenergic neuronal dysfunction may therefore constitute an important pharmacological target for the treatment of non-motor symptoms in PD. Furthermore, epidemiologic studies have demonstrated that long term treatment with beta-agonists may slow the progression of PD[3,4].This study aimed to assess the safety, tolerability and CNS effects of β-agonists in healthy volunteers (HV) and PD patients.
Method: In Part A, HV received single doses of salbutamol, clenbuterol, pindolol and placebo (randomized cross-over trial, n=16). In Part B (cross-over trial, n=16) and C (parallel trial, n=12 (8 treatment, 4 placebo)), clenbuterol and placebo were administered for 7 days to HV and PD patients. In all parts, safety, tolerability and CNS (by a validated test battery including EEG) effects were evaluated. Outcome variables are expressed as Least Square Means [95%CI].
Results: Single dose salbutamol 32mg, pindolol 60mg and clenbuterol 160ug was safe. Interim safety and CNS results of Part A led to choosing clenbuterol for multiple doses. In Part A, clenbuterol increased the number of correctly recalled words during the immediate recall trial 1 of Visual Verbal Learning Task (1.3 words [0.1 – 2.6]). Clenbuterol was safe up to 80ug for 7 days in HVs and increased saccadic peak velocity (14.58 degrees/s [2.73;26.44]) and adaptive tracker performance (1.58% [0.22;2.94]), while saccadic reaction time was decreased (-0.016s [-0.01;-0.01]). Also, clenbuterol increased EEG delta power in the occipital regions with eyes open and closed. In PD patients, clenbuterol was safe, well tolerated and increased heart rate. The sample size was too small to conclude on CNS effects of clenbuterol in PD.
Conclusion: In HV, clenbuterol penetrated the blood-brain barrier, as demonstrated by EEG and showed positive effects on some cognitive domains. In PD patients, clenbuterol was well tolerated and increased heart rate. More studies are needed to determine the effects of long-term treatment with clenbuterol.
References: 1. Vermeiren Y, De Deyn PP. Targeting the norepinephrinergic system in Parkinson’s disease and related disorders: The locus coeruleus story. Neurochem Int. 2017;102:22-32. doi:10.1016/j.neuint.2016.11.009 2. Nahimi A, Sommerauer M, Kinnerup MB, et al. Noradrenergic Deficits in Parkinson Disease Imaged with (11)C-MeNER. J Nucl Med. 2018;59(4):659-664. doi:10.2967/jnumed.117.190975 3. Mittal S, Bjørnevik K, Im DS, et al. β2-Adrenoreceptor is a regulator of the α-synuclein gene driving risk of Parkinson’s disease. Science (80- ). 2017;357(6354):891-898. doi:10.1126/science.aaf3934 4. Gronich N, Abernethy DR, Auriel E, Lavi I, Rennert G, Saliba W. β2-adrenoceptor agonists and antagonists and risk of Parkinson’s disease. Mov Disord. 2018;33(9):1465-1471. doi:10.1002/mds.108
To cite this abstract in AMA style:
P. Eijsvogel, S. Prins, L. Moss, L. Borghans, B. van Kraaij, E. van Brummelen, E. Klaassen, R. Martin, E. Bautista, A. Ford, GJ. Groeneveld, G. Vargas. Safety, tolerability and CNS effects after single and multiple doses of β-agonists in healthy volunteers and patients with Parkinson’s disease [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/safety-tolerability-and-cns-effects-after-single-and-multiple-doses-of-%ce%b2-agonists-in-healthy-volunteers-and-patients-with-parkinsons-disease/. Accessed May 15, 2025.« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/safety-tolerability-and-cns-effects-after-single-and-multiple-doses-of-%ce%b2-agonists-in-healthy-volunteers-and-patients-with-parkinsons-disease/