{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T07:52:56Z","timestamp":1782978776699,"version":"3.54.5"},"reference-count":54,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T00:00:00Z","timestamp":1719878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>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\u2010clinical models, \u03b2\u2010adrenoceptor (\u03b2\u2010AR) 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\u2010penetrant \u03b2<jats:sub>2<\/jats:sub>\u2010AR agonist, clenbuterol, in healthy volunteers (HV) and patients with mild cognitive impairment (MCI) or Parkinson's disease (PD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study evaluated the safety and effects on cerebral activity of the oral, brain\u2010penetrant, \u03b2<jats:sub>2<\/jats:sub>\u2010AR agonist clenbuterol (20\u2013160\u2009\u03bcg) in healthy volunteers and patients with MCI or PD. Regional CBF, which is tightly coupled to glucose metabolism, was measured by arterial spin labelling MRI in 32 subjects (25\u2009HV and 8 MCI or PD) across five cohorts. In some cohorts, low doses of nadolol (1\u20135\u00a0mg), a \u03b2\u2010AR antagonist with minimal brain penetration, were administered with clenbuterol to control peripheral \u03b2<jats:sub>2<\/jats:sub>\u2010AR responses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant, dose\u2010dependent increases in rCBF were seen in multiple brain regions, including hippocampus, amygdala and thalamus, following the administration of clenbuterol to HVs (mean changes from baseline in hippocampal rCBF of \u22121.7%, 7.3%, 22.9%, 28.4% 3\u00a0h after 20, 40, 80 and 160\u2009\u03bcg clenbuterol, respectively). In patients with MCI or PD, increases in rCBF following 80\u2009\u03bcg clenbuterol were observed both without and with 5\u00a0mg nadolol (in hippocampus, 18.6%\/13.7% without\/with nadolol). Clenbuterol was safe and well\u2010tolerated in all subjects; known side effects of \u03b2<jats:sub>2<\/jats:sub>\u2010agonists, including increased heart rate and tremor, were mild in intensity and were blocked by low\u2010dose nadolol.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The effects of clenbuterol on rCBF were evident both in the absence and presence of low\u2010dose nadolol, suggesting central nervous system (CNS) involvement. Concomitant inhibition of the peripheral effects of clenbuterol by nadolol confirms that meaningful \u03b2<jats:sub>2<\/jats:sub>\u2010AR antagonism in the periphery was achieved without interrupting the central effects of clenbuterol on rCBF.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16160","type":"journal-article","created":{"date-parts":[[2024,7,2]],"date-time":"2024-07-02T11:09:20Z","timestamp":1719918560000},"page":"2638-2651","source":"Crossref","is-referenced-by-count":3,"title":["Effects on cerebral blood flow after single doses of the \u03b2<sub>2<\/sub> agonist, clenbuterol, in healthy volunteers and patients with mild cognitive impairment or Parkinson's disease"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6137-7931","authenticated-orcid":false,"given":"Thomas","family":"Lodeweyckx","sequence":"first","affiliation":[{"name":"Center for Clinical Pharmacology, Department of Pharmaceutical and Pharmacological Sciences Catholic University 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