α-adrenergic receptor

Pictured: Concept art showing an elderly woman overlaid with an illustration of a brain/iStock, boonstudio Drugs commonly used for the treatment of enlarged prostate may also help lower the risk of dementia with Lewy bodies, according to a new observational study from the University of Iowa Health Care. Drawing from Merative MarketScan, one of the largest proprietary U.S. healthcare claims databases, University of Iowa researchers identified more than 643,000 men who were starting treatment for benign prostatic hyperplasia with one of six common therapies. Three of these drugs fell under the class of α-1 adrenergic receptor antagonists, better known as α-blockers, which work by inhibiting the contraction of smooth muscles. The researchers focused on terazosin, which is sold by Abbott under the brand name Hytrin, doxazosin, which is marketed by Pfizer as Cardura, and alfuzosin, which is branded as Uroxatral by Sanofi. Alpha-blocker drugs are known to have a unique side effect: they activate a key enzyme involved in the production of ATP, which is the molecular form of cellular energy. In the brain, these drugs can help boost the production of energy and fight neurodegeneration, the University of Iowa scientists hypothesized. As active comparators, the researchers also followed men in Merative MarketScan who were being treated with tamsulosin or with the 5α-reductase inhibitors (5ARI) finasteride and dutasteride, all of which are not known to affect energy production in the brain. The men included in the study had no history of dementia with Lewy bodies (DLB). Participants were then followed until they exited the database or until they developed DLB. After an average follow-up of around three years, the study found that men who were initiated on the three alpha-blocker drugs were 40% less likely to develop DLB than comparators who were on tamsulosin. Compared with men whose enlarged prostates were being treated with 5ARI agents, the risk of DLBA was 27% lower in those taking alpha-blocker drugs. Both effects were statistically significant. By contrast, DLB had a statistically similar likelihood of developing in men being managed with tamsulosin and 5ARIs. These results were robust to several sensitivity analyses, according to researchers. The University of Iowa scientists published their findings Wednesday in Neurology, the medical journal of the American Academy of Neurology. “If terazosin and these similar medications can help slow this progression—if not outright preventing the disease—this would be important to preserving cognitive function and quality of life in people with DLB,” Jacob Simmering, assistant professor of internal medicine at the University of Iowa and lead study author, said in a statement. However, the researchers caution that the study is simply observational in design and only shows that there is a statistical correlation between the use of alpha-blocker drugs and the reduced risk of DLB. It does not establish causation nor does it show any directionality of association, they said. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

WEDNESDAY, June 19, 2024 -- Men taking α-1 adrenergic receptor antagonists terazosin, doxazosin, and alfuzosin (Tz/Dz/Az) seem to have a lower risk for dementia with Lewy bodies (DLB), according to a study published online June 19 in Neurology . Alexander Hart, M.D., M.P.H., from the University of Michigan in Ann Arbor, and colleagues used a new-user active comparator design in the Merative Marketscan database to identify men with no history of DLB who were newly initiated on Tz/Dz/Az or two comparator medications (α-1 adrenergic receptor antagonist tamsulosin or 5α-reductase inhibitor [5ARI]) to examine the potential neuroprotective effects of Tz/Dz/Az. The researchers found that the risk for developing DLB was lower for men who were newly started on Tz/Dz/Az than those taking tamsulosin or 5ARI (hazard ratios, 0.60 and 0.73, respectively), while the risk was similar for men taking tamsulosin versus 5ARI. The results were robust to sensitivity analyses. "More research is needed to follow people over time and determine whether there is a cause-and-effect relationship here, but it is promising to think that these drugs could have a protective effect on this disease that will likely affect a larger number of people as the population ages," coauthor Jacob E. Simmering, Ph.D., of the University of Iowa in Iowa City, said in a statement.

Both Minerva and Karuna’s candidates aim to avoid blocking dopamine receptors, thereby reducing side effects seen with current antipsychotic therapies. Image credit: Shutterstock/Kubko. A potential landmark year for schizophrenia treatments has got off to a rocky start, after the US Food and Drug Administration (FDA) declined to approve Minerva Neurosciences’ roluperidone for the treatment of negative symptoms in patients with schizophrenia. It’s the second snag Minerva has encountered with the FDA, after the agency shunned a review of an initial marketing application for the serotonin, sigma, and α-adrenergic receptor-blocking drug in 2022. The FDA’s complete response letter raised four clinical decencies from Minerva’s new drug application (NDA), according to a 27 February press release. Shares in the company slid by over 50% at market open compared to a pre-announcement market close on 26 February. The FDA alluded to the MIN-101C03 study, saying that although the primary efficacy endpoint met statistical significance, more evidence is needed to back up the drug’s effectiveness. The agency added that more data is needed to demonstrate the improvement patients saw was clinically meaningful. See Also: Every Cure receives ARPA-H grant for drug repurposing Biotechs heed political headwinds for drug pricing negotiations and partnerships Other shortcomings included the lack of data on concomitant antipsychotic administration and an inadequate number of subjects exposed to 64mg roluperidone – the proposed dose – for at least a year. Minerva’s CEO Dr Remy Luthringer said the biopharma is “disappointed” at the FDA’s rejection, adding that it has requested a meeting with the agency to discuss the feedback. The company will now need to conduct a further study to address the deficiencies if it wishes to secure FDA approval for the drug. Additional readouts from patients taking the drug alongside antipsychotic medications – used to prove roluperidone’s clinically meaningful benefit – and long-term safety data will also need to be submitted. Dr Luthringer added: “We believe that roluperidone is a safe and effective therapy for negative symptoms of schizophrenia and we will review FDA’s feedback and consider our potential paths forward, including continuing to work closely with the FDA and providing any additional information as needed.” Minerva designed roluperidone to not directly block the action of dopaminergic receptors. Dopaminergic receptors are the main target of current antipsychotic therapies for patients with schizophrenia, but this comes with side effects. Following Minerva’s rejection, all eyes will now be on Karuna Therapeutics , which could have its drug approved for adults with schizophrenia in late 2024. The US biotech’s highly anticipated candidate KarXT (xanomeline-trospium) is a dual M1/M4 muscarinic agonist that could reduce both positive and negative symptoms of the neurological disorder. Similar to Minerva, Karuna has gone down the “non-dopamine blocking” route.  The Prescription Drug User Fee Act (PDUFA) date for KarXT is 26 September 2024. If approved, the drug would represent a new class of medication on offer to those with schizophrenia. The promise of Karuna’s treatment is clear, with the company acquired by BMS for $14bn in December 2023. There are also key Phase III trial readouts for late-stage schizophrenia candidates in 2024. Schizophrenia affects around 24 million people globally, according to the World Health Organization. The schizophrenia drug market is forecast to grow to $21.2bn across 68 global markets, according to a 2022 report by GlobalData . GlobalData is the parent company of Pharmaceutical Technology.