Beta2-adrenoreceptor agonists and long-term risk of Parkinson's disease

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Beta2-adrenergic agonists, also known as adrenergic β2 receptor agonists, are a class of drugs that act on the β2 adrenergic receptor. Like other β adrenergic agonists, they cause smooth muscle relaxation leading dilatation of bronchial passages, vasodilation in muscle and liver, relaxation of uterine muscle, and release of insulin. enter image description here They are primarily used to treat asthma and other pulmonary disorders, such as Chronic obstructive pulmonary disease (COPD). Yet β2 agonists are used by athletes and bodybuilders as anabolic performance-enhancing drugs. They are also used illegally to try to promote the growth of livestock.

Scientists from Bergen, Norway, were interested in the association between Parkinson's disease and the use of beta2-adrenoreceptor (β2AR) agonists vary among groups of short-, long-, and ultra-long-acting β2AR agonists (SABA, LABA, and ultraLABA).

There is evidence supporting the use of β2AR agonists in synucleinopathies is rapidly growing. Molecular and immunological data suggest that adrenergic stimulation may decrease both α-synuclein (α-syn) deposition and pro-inflammatory/neurotoxic molecules release.

Small open-label clinical trials including a total number of 25 Parkinson's disease (PD) patients, in which the β2AR agonist salbutamol was added to levodopa, suggest a promising symptomatic benefit.

However, other mechanisms might explain this apparent association. Some persons with prodromal PD symptoms of anxiety and tremor might avoid β2AR agonists due to the potential of these drugs to exacerbate such symptoms. A study in a UK cohort of 2,430,884 patients found that apparent association of β2-agonists with a decreased risk of PD was likely the result of reverse causality rather than a biological effect of these drugs on the risk of PD.

In the Norwegian study the scientists searched for Parkinson disease cases and prescriptions in a population of 3.2 million people. This was facilitated by the fact that in Norway, drugs for treating certain diseases, such as PD, asthma, and chronic obstructive pulmonary disease (COPD), are covered by the national insurance system, and the reimbursement codes indicate the disease for which the medicine was prescribed.

Beta2-adrenergic agonists can be classified in short-acting β2 agonists (SABAs), long-acting β2 agonists (LABAs), and ultra-long-acting β2 agonists (ultraLABA). A dose-response analysis was conducted on β2AR agonists and separately on groups of SABA, LABA, and ultraLABA.

Evidence for a negative association between β2AR agonists and PD. All three subgroups of β2AR agonists remained inversely associated with PD risk in the fully adjusted model and after stratification by indication of use, with ultraLABA displaying the overall strongest association. The observed dose-response relationships are also consistent with a protective effect.

There is an inverse association between β2AR agonists and PD attributed to smoking habits. This is an important source of potential bias. β2AR agonists are commonly used for conditions associated with smoking, such as COPD, and smoking has consistently been associated with a reduced PD risk.

Adjusting for level of education in the present study did not notably influence the risk estimates. These results were surprising given the markedly decreased risk of PD among individuals with lowest education who smoke more and use more β2AR agonists, than those with highest education after adjustment for sex and age.

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