Pramipexole Dihydrochloride

iStock, Irina Tatsina Alto Neuroscience is advancing a depression drug based on the dopamine agonist pramipexole, which an independent study has found to help boost feelings of pleasure in patients with mood disorders. The dopamine agonist pramipexole could help restore the ability to feel pleasure in patients with mood disorders, bolstering the case for Alto Neuroscience’s depression drug that is based on the same active compound, according to an independent study conducted by a Swedish university. Conducted at the Lund University in Sweden, the randomized, double-blinded and placebo-controlled PRIME-PRAXOL study enrolled more than 80 patients with major depressive disorder (MDD), bipolar depression or dysthymia, a condition characterized by persistent low mood but not enough to meet the definition of MDD. The study looked specifically at pramipexole, a dopamine agonist that works by exerting antidepressant effects across the brain. Pramipexole is approved as Boehringer Ingelheim’s Mirapex for Parkinson’s disease and restless leg syndrome, but Alto is advancing an investigational pramipexole-based treatment called ALTO-207, which combines fixed doses of the dopamine agonist with the antiemetic ondansetron. This combo, currently in mid-stage trials, allows higher doses at a more rapid titration by preventing side effects that would otherwise have been dose-limiting, Alto said in a news release on Monday . Results of the independent study were published Friday in Nature Medicine and showed that pramipexole significantly improved anhedonia scores on the Snaith-Hamilton Pleasure Scale . This tool, commonly known by the shorthand SHAPS, measures how much pleasure a patient derives from common daily activities, such as watching TV, spending time with family and friends or engaging in hobbies. The independent study also found that pramipexole had stronger anhedonia benefits in patients with MDD as compared with those who had dysthymia, Alto said on Monday, presenting the paper’s findings. Pramipexole’s improvements to anhedonia were maintained throughout six months of observation. Alto “is looking to disrupt the [central nervous system] paradigm by leveraging precision psychiatry” to maximize the success of its trials, Jefferies told investors on Monday, referring to the company’s use of biomarkers to guide the development process. The firm expects the biotech’s stock to “move significantly higher” if any of its Phase 2b readouts next year deliver promising findings. Alto has several of these mid-stage studies running across several indications, including MDD and bipolar depression. In April, the company launched a Phase 2b study of ALTO-207 in treatment-resistant depression (TRD). Across these studies, however, “we are particularly keen on ALTO-207’s pivotal Phase IIb dataset” in TRD, expected to come in the back half of 2027, Jefferies said. On this front, the readout from the independent PRIME-PRAXOL study “instills confidence” in ALTO-207’s success, the analysts added. Depression 5 Depression Trials That Failed in 2025 The R&D pipeline for depression therapies faced a demoralizing 2025 as five high-pro including KOR antagonists by Johnson & Johnson and Neumora Therapeutics, flunked late-stage clinical trials, underscoring the persistent challenges of CNS drug development. December 8, 2025 · 6 min read · Ben Hargreaves Read more

– Independent, peer-reviewed, placebo-controlled trial conducted by Lund University showed pramipexole significantly reduced anhedonia (primary endpoint, Hedges’ g=0.62, p=0.006) – – Benefit extended to independent anhedonia and apathy measures (DARS, AES-S) and was sustained through six months of open-label treatment – – Findings reinforce the dopaminergic mechanism underlying ALTO-207; potentially pivotal Phase 2b trial in treatment-resistant depression is ongoing with data expected in 2H 2027 – MOUNTAIN VIEW, Calif.--(BUSINESS WIRE)-- $anro #cns --Alto Neuroscience, Inc. (“Alto”) (NYSE: ANRO) today highlighted the publication in Nature Medicine of PRIME-PRAXOL , an independent, randomized, double-blind, placebo-controlled trial of the dopamine agonist pramipexole in patients with mood disorders and clinically significant anhedonia. The study was conducted and independently funded by investigators at Lund University, Sweden. Adults with elevated baseline anhedonia symptoms with a diagnosis of major depressive disorder, dysthymia (chronic low mood, but not meeting MDD diagnostic criteria), or bipolar depression were randomized to flexible-dose pramipexole or placebo, added to ongoing treatment, for nine weeks, followed by a six-month open-label extension period. On the primary endpoint, pramipexole reduced anhedonia significantly more than placebo on the Snaith–Hamilton Pleasure Scale (mean difference −4.04; 95% CI −6.89 to −1.18; p=0.006; Hedges’ g=0.62 - Hedges’ g is a standardized measure of treatment effect similar to Cohen’s D), with significant improvements on independent measures of anhedonia (DARS; p=0.008) and apathy (AES-S; p<0.001) with improvements maintained through a six-month open-label treatment period. Importantly, the publication also included a post-hoc analysis which found that a diagnosis of MDD, compared to the milder affective condition of dysthymia, showed a significant association with a greater change in SHAPS at week 9 in a regression analysis (p=0.038). In an analysis not published in the Nature Medicine piece, the MDD subgroup demonstrated a significantly larger effect on SHAPS at week 9 (Hedges’ g=0.99) and a significant effect on the Hamilton Depression Rating Scale (HDRS-6) (Hedges’ g=0.64). “Anhedonia is among the most disabling yet poorly addressed dimensions of depression, and it is the domain dopaminergic mechanisms are perhaps best positioned to address,” said Amit Etkin, M.D., Ph.D., founder and chief executive officer of Alto Neuroscience. “These Nature Medicine results add independent, peer-reviewed high-pro — alongside PAX-D in The Lancet Psychiatry — for the effects of pramipexole, the active dopaminergic component of ALTO-207. Notably, the high nausea rate in this trial illustrates the precise tolerability limitation ALTO-207 is engineered to overcome — aiming to unlock this promising mechanism for a broader patient population. We are very encouraged by the results from this trial, further strengthening the scientific foundation for ALTO-207 as we advance our potentially pivotal Phase 2b trial in treatment-resistant depression.” Consistent with prior studies, adverse events were common in the pramipexole arm despite a slow titration schedule — including nausea in roughly 60% of participants, along with sleep disturbance, dizziness, fatigue, and anxiety — reflecting the dose-limiting tolerability that has long constrained pramipexole’s use. ALTO-207 pairs pramipexole with the antiemetic ondansetron specifically aimed at mitigating these effects and enabling faster titration to therapeutic doses. “Conventional antidepressants have little effect on the brain’s reward systems, leaving depressed patients with anhedonia having marked symptoms. With this study, the Lund group adds to the other recent work demonstrating that pramipexole greatly reduces this anhedonic burden,” said Alan Schatzberg, MD, Kenneth T. Norris Professor of Psychiatry and Behavioral Sciences at Stanford University School of Medicine. “What stands out in this study is the consistency of the findings — pramipexole improved both the consummatory and motivational dimensions of anhedonia, on multiple independent scales, and with good durability. Matching a dopaminergic treatment to patients defined by anhedonia, and potentially related reward-circuit dysfunction, is the kind of mechanism-led approach the field needs.” The published findings across the PRIME-PRAXOL study are consistent with the broader evidence supporting ALTO-207, including PAX-D (Cohen’s d=0.87 versus placebo at 12 weeks in treatment-resistant depression) and a meta-analysis of pramipexole in depression (Hedges’ g=0.64). About ALTO-207 ALTO-207 is a fixed-dose combination of pramipexole, a dopamine D3-preferring D3/D2 agonist, approved for the treatment of Parkinson’s disease with demonstrated antidepressant effect, and ondansetron, an antiemetic, selective 5-HT3 receptor antagonist. As a fixed-dose combination, ALTO-207 is designed to enable rapid titration and higher dosing by mitigating the dose-limiting adverse events typically experienced with pramipexole. ALTO-207 is being developed to address the significant unmet need for patients with treatment resistant depression. In a randomized, placebo-controlled Phase 2a clinical trial evaluating ALTO-207 in 32 patients with depression ALTO-207 met primary and secondary endpoints demonstrating significantly greater improvements on MADRS compared to placebo. Patients randomized to receive ALTO-207 reached a mean dose of 4.1mg per day. ALTO-207 was well tolerated in the maintenance period of the study with an adverse event rate similar to placebo. About Alto Neuroscience Alto Neuroscience is a clinical-stage biopharmaceutical company with a mission to redefine psychiatry by leveraging neurobiology to develop personalized and highly effective treatment options. Alto’s Precision Psychiatry Platform™ measures brain biomarkers by analyzing EEG activity, neurocognitive assessments, wearable data, and other factors to better identify which patients are more likely to respond to Alto product candidates. Alto’s clinical-stage pipeline includes novel drug candidates in bipolar depression, major depressive disorder, treatment resistant depression, schizophrenia, and other mental health conditions. For more information, visit or follow Alto on X . Forward-Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “look forward,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding Alto’s expectations about the potential benefits, activity, effectiveness, tolerability and safety of its product candidates and Precision Psychiatry Platform (“Platform”); statements regarding Alto’s expectations for the design, timing, and results of its Phase 2b and planned Phase 3 trials of ALTO-207; Alto’s expectations with regard to the general design and results of its research and development programs and clinical trials, including the timing of enrollment and the timing and availability of data from such trials; Alto’s clinical development plans for its product candidates, including the timing or likelihood of approvals for its product candidates; Alto’s business strategy, financial position, including anticipated cash runway, and the sufficiency of its financial resources to fund its operations through expected milestones; and other statements that are not historical fact. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including uncertainties inherent in the initiation, progress and completion of clinical trials and development of Alto’s product candidates; availability and timing of results from clinical trials; the risk that clinical trials may have unsatisfactory outcomes; the risk that Alto’s projections regarding its financial position and expected cash runway are inaccurate or that its conduct of its business requires more cash than anticipated; and other important factors, any of which could cause Alto’s actual results to differ from those contained in the forward-looking statements, which are described in greater detail in the section titled “Risk Factors” in Alto’s Annual Report on Form 10-K for the fiscal year ended December 31, 2025 filed with the Securities and Exchange Commission (“SEC”) as well as in other filings Alto may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Alto expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as required by law. Availability of Information on Alto’s Website Alto routinely uses its investor relations website to post presentations to investors and other important information, including information that may be material. Accordingly, Alto encourages investors and others interested in Alto to review the information it makes public on its investor relations website. Contacts Investor and Media Contact: Nick Smith investors@altoneuroscience.com media@altoneuroscience.com