Recent studies related angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers to possible neuroprotective effects. Little is known about neuroprotection of angiotensin II (AT II) antagonists or beta-blockers.
To explore the association between antihypertensive drug use and the risk of developing a first-time diagnosis of Parkinson disease (PD).
This was a case-control analysis within the UK-based General Practice Research Database. Cases were >or=40 years of age with an incident PD diagnosis between 1994 and 2005. We matched one control to each PD case on age, sex, general practice, index date, and duration of previous history in the database. We assessed antihypertensive drug use by timing and by exposure duration. We calculated ORs using conditional logistic regression, adjusted for body mass index, smoking, and various cardiovascular, metabolic, and psychiatric diseases and dementia.
We identified 3,637 cases with a first-time diagnosis of idiopathic PD and an equal number of matched controls. As compared to nonuse of antihypertensive drugs, the adjusted OR for current use of >or=30 prescriptions was 1.08 (95% CI 0.85 to 1.37) for ACE inhibitors, 0.91 (95% CI 0.41 to 2.00) for AT II antagonists, 1.16 (95% CI 0.95 to 1.41) for beta-blockers, and 0.77 (95% CI 0.63 to 0.95) for calcium channel blockers.
Current long-term use of calcium channel blockers was associated with a significantly reduced risk of a Parkinson disease diagnosis, while the risk was not materially altered for users of angiotensin converting enzyme inhibitors or beta-blockers and, with less statistical precision, for users of angiotensin II antagonists.
"Disease duration was not associated to increased risk of constipation, when corrected for age and pharmacological treatment. The percentage of PD patients taking beta-blockers in our cohort was in line with larger epidemiological studies  and their absolute number was sufficiently large to support the statistical conclusions. "
"LTCC blockers are already well-established drugs, and are commonly prescribed to treat hypertension in clinical practice (Epstein et al., 2007; Exner et al., 2012; Coca et al., 2013). Indeed, retrospective epidemiological studies demonstrated that systemic administration of blood–brain-barrier permissive LTCC blockers of the DHP-type (like isradipine) reduce the relative risk for developing PD of about 30 % (Becker et al., 2008; Ritz et al., 2010; Simuni et al., 2010; Marras et al., 2012; Pasternak et al., 2012; Parkinson Study, 2013). However, reliable prospective studies are still missing, and not all epidemiologic studies report PD-protective effects of LTCC blockers (Ton et al., 2007; Louis et al., 2009; Simon et al., 2010). "
[Show abstract][Hide abstract] ABSTRACT: Dopamine (DA) releasing midbrain neurons are essential for multiple brain functions, such as voluntary movement, working memory, emotion and cognition. DA midbrain neurons within the substantia nigra (SN) and the ventral tegmental area (VTA) exhibit a variety of distinct axonal projections and cellular properties, and are differentially affected in diseases like schizophrenia, attention deficit hyperactivity disorder, and Parkinson's disease (PD). Apart from having diverse functions in health and disease states, DA midbrain neurons display distinct electrical activity patterns, crucial for DA release. These activity patterns are generated and modulated by specific sets of ion channels. Recently, two ion channels have been identified, not only contributing to these activity patterns and to functional properties of DA midbrain neurons, but also seem to render SN DA neurons particularly vulnerable to degeneration in PD and its animal models: L-type calcium channels (LTCCs) and ATP-sensitive potassium channels (K-ATPs). In this review, we focus on the emerging physiological and pathophysiological roles of these two ion channels (and their complex interplay with other ion channels), particularly in highly vulnerable SN DA neurons, as selective degeneration of these neurons causes the major motor symptoms of PD.
"Adult SNc DA neurons can compensate for L-type Ca2+ channel antagonism and continue pacemaking (Chan et al., 2007), and mice do not show obvious motor, learning, or cognitive deficits when treated with L-type Ca2+ channel antagonists (Bonci et al., 1998), suggesting that these compounds do not alter the functional activity of SNc DA neurons. Indeed, several studies in humans indicate that these compounds diminish the risk of developing PD (Becker et al., 2008; Ritz et al., 2010; Pasternak et al., 2012). However, they do not seem to slow progression of PD (Marras et al., 2012), maybe because of their relatively poor potency against Cav1.3 "
[Show abstract][Hide abstract] ABSTRACT: Parkinson's disease (PD) is a major health problem affecting millions of people worldwide. Recent studies provide compelling evidence that altered Ca(2) (+) homeostasis may underlie disease pathomechanism and be an inherent feature of all vulnerable neurons. The downstream effects of altered Ca(2) (+) handling in the distinct subcellular organelles for proper cellular function are beginning to be elucidated. Here, we summarize the evidence that vulnerable neurons may be exposed to homeostatic Ca(2) (+) stress which may determine their selective vulnerability, and suggest how abnormal Ca(2) (+) handling in the distinct intracellular compartments may compromise neuronal health in the context of aging, environmental, and genetic stress. Gaining a better understanding of the varied effects of Ca(2) (+) dyshomeostasis may allow novel combinatorial therapeutic strategies to slow PD progression.
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