MIRA Pharmaceuticals Announces Positive Discovery of Ketamir-2’s Selective NMDA Binding Mechanism of Action
MIRA Pharmaceuticals (NASDAQ:MIRA) has announced positive preclinical data for its novel oral ketamine analog, Ketamir-2, bringing it closer to a potential IND submission this year. The latest findings reveal that Ketamir-2 is a selective inhibitor of the NMDA receptor, specifically interacting at the PCP-binding site with 30-50-fold lower affinity compared to ketamine. This selectivity may lead to reduced side effects and an improved safety profile.
Toxicology studies in rats and dogs have shown no toxicity at high doses, indicating an excellent safety margin. Ketamir-2 also demonstrates pronounced antidepressant and anxiolytic activities at lower doses. The compound's unique selectivity and robust safety data enhance its potential as a transformative treatment for neurological and neuropsychiatric disorders, including depression, treatment-resistant depression, and PTSD.
MIRA Pharmaceuticals (NASDAQ:MIRA) ha annunciato dati preclinici positivi per il suo nuovo analogico orale di ketamina, Ketamir-2, avvicinandosi così a una potenziale presentazione della domanda IND quest'anno. I risultati più recenti rivelano che Ketamir-2 è un inibitore selettivo del recettore NMDA, interagendo specificamente con il sito di legame PCP con un'affinità 30-50 volte inferiore rispetto alla ketamina. Questa selettività potrebbe portare a effetti collaterali ridotti e a un profilo di sicurezza migliorato.
Studi di tossicologia su ratti e cani hanno mostrato nessuna tossicità a dosi elevate, indicando un eccellente margine di sicurezza. Ketamir-2 dimostra anche pronunciate attività antidepressivi e ansiolitiche a dosi più basse. L'uniqueness della selettività del composto e i robusti dati di sicurezza ne aumentano il potenziale come trattamento trasformativo per disturbi neurologici e neuropsichiatrici, inclusa la depressione, la depressione resistente al trattamento e il PTSD.
MIRA Pharmaceuticals (NASDAQ:MIRA) ha anunciado datos preclínicos positivos para su nuevo análogo oral de ketamina, Ketamir-2, acercándolo a una posible presentación de IND este año. Los hallazgos más recientes revelan que Ketamir-2 es un inhibidor selectivo del receptor NMDA, interactuando específicamente en el sitio de unión PCP con una afinidad de 30 a 50 veces menor en comparación con la ketamina. Esta selectividad puede conducir a efectos secundarios reducidos y a un perfil de seguridad mejorado.
Los estudios de toxicología en ratas y perros han mostrado ninguna toxicidad a altas dosis, lo que indica un excelente margen de seguridad. Ketamir-2 también demuestra pronunciadas actividades antidepresivas y ansiolíticas a dosis más bajas. La selectividad única del compuesto y los sólidos datos de seguridad aumentan su potencial como un tratamiento transformador para trastornos neurológicos y neuropsiquiátricos, incluidos la depresión, la depresión resistente al tratamiento y el PTSD.
MIRA 제약 (NASDAQ:MIRA)는 새로운 경구 케타민 유사체인 Ketamir-2에 대한 긍정적인 전임상 데이터를 발표하였으며, 올해 잠재적인 IND 제출에 한 발 더 다가섰습니다. 최신 연구 결과에 따르면 Ketamir-2는 NMDA 수용체의 선택적 억제제로, PCP 결합 부위에서 케타민보다 30-50배 낮은 친화도로 상호작용합니다. 이러한 선택성은 부작용 감소 및 개선된 안전성 프로파일로 이어질 수 있습니다.
쥐와 개에서 실시한 독성 연구에 따르면 고용량에서 독성이 없음을 보였으며, 이는 우수한 안전 여유를 나타냅니다. Ketamir-2는 또한 낮은 용량에서 뚜렷한 항우울 및 항불안 작용을 나타냅니다. 이 화합물의 독특한 선택성과 강력한 안전성 데이터는 우울증, 치료 저항성 우울증 및 PTSD를 포함한 신경학적 및 신경정신적 장애에 대한 혁신적인 치료법으로서의 잠재력을 높여줍니다.
MIRA Pharmaceuticals (NASDAQ:MIRA) a annoncé des données précliniques positives pour son nouvel analogue oral de kétamine, Ketamir-2, le rapprochant d'une soumission potentielle d'IND cette année. Les dernières découvertes révèlent que Ketamir-2 est un inhibiteur sélectif du récepteur NMDA, interagissant spécifiquement au site de liaison PCP avec une affinité 30 à 50 fois inférieure à celle de la kétamine. Cette sélectivité pourrait mener à des effets secondaires réduits et à un profil de sécurité amélioré.
Des études de toxicologie chez le rat et le chien n'ont montré aucune toxicité à des doses élevées, indiquant une excellente marge de sécurité. Ketamir-2 démontre également des activités antidépresseurs et anxiolytiques prononcées à des doses plus faibles. La sélectivité unique du composé et des données de sécurité robustes renforcent son potentiel en tant que traitement transformateur pour les troubles neurologiques et neuropsychiatriques, y compris la dépression, la dépression résistante au traitement et le PTSD.
MIRA Pharmaceuticals (NASDAQ:MIRA) hat positive präklinische Daten für sein neuartiges orales Ketamin-Analogon Ketamir-2 bekannt gegeben, was es näher an eine mögliche IND-Einreichung in diesem Jahr bringt. Die neuesten Ergebnisse zeigen, dass Ketamir-2 ein selektiver Inhibitor des NMDA-Rezeptors ist, der spezifisch am PCP-Bindungsstelle mit 30-50-fach geringerer Affinität im Vergleich zu Ketamin interagiert. Diese Selektivität könnte zu reduzierten Nebenwirkungen und einem verbesserten Sicherheitsprofil führen.
Toxikologiestudien an Ratten und Hunden haben keine Toxizität bei hohen Dosen gezeigt, was auf eine hervorragende Sicherheitsmarge hinweist. Ketamir-2 zeigt auch ausgeprägte antidepressiv und anxiolytische Aktivitäten bei niedrigeren Dosen. Die einzigartige Selektivität des Verbindungsstoffs und die robusten Sicherheitsdaten erhöhen sein Potenzial als transformative Behandlung für neurologische und neuropsychiatrische Störungen, einschließlich Depression, therapieresistente Depression und PTSD.
- Ketamir-2 shows selective inhibition of NMDA receptor, potentially reducing side effects
- Toxicology studies reveal no toxicity at high doses, indicating excellent safety margin
- Ketamir-2 demonstrates antidepressant and anxiolytic activities at low doses
- The compound shows superior brain penetration and bioavailability
- Positive preclinical data brings MIRA closer to potential IND submission this year
- None.
Insights
As a neuropharmacology expert, I find the selective NMDA binding mechanism of Ketamir-2 particularly intriguing. The 30-50-fold lower affinity to the PCP site compared to ketamine is a significant advancement. This could potentially reduce the risk of dissociative side effects while maintaining therapeutic efficacy.
The selectivity for the NMDA receptor's PCP-binding site, without interacting with opioid receptors, dopamine and serotonin transporters, or acetylcholine receptors, is a game-changer in the field of neuropsychiatric treatments. This unique pharmacological profile could lead to a more targeted approach in treating conditions like depression and PTSD, potentially minimizing off-target effects.
However, it's important to note that while preclinical data is promising, the true test will be in human clinical trials. The transition from animal models to human subjects can often reveal unexpected challenges or side effects. As we move forward, it will be essential to closely monitor how this selectivity translates to therapeutic outcomes and safety profiles in humans.
From a clinical perspective, the potential of Ketamir-2 is exciting. The enhanced safety profile, with no toxicity observed at high doses in animal studies, is particularly promising. This could potentially allow for more flexible dosing strategies in treating complex psychiatric conditions like treatment-resistant depression.
The improved brain penetration due to Ketamir-2 not being a substrate for P-glycoprotein is another significant advantage. This could lead to more consistent therapeutic effects and potentially lower required doses, further enhancing the safety profile.
However, we must remain cautious. While the preclinical data is encouraging, the real test will be in human trials. The unique selectivity of Ketamir-2 might lead to unexpected effects in human subjects, both positive and negative. As we move towards clinical trials, it will be important to design studies that can fully elucidate the drug's effects on mood, cognition and overall mental health in diverse patient populations.
If Ketamir-2 can deliver on its promise of rapid-acting antidepressant effects with a better safety profile than current options, it could indeed represent a significant advancement in our treatment arsenal for severe psychiatric disorders.
From an investment perspective, MIRA Pharmaceuticals' progress with Ketamir-2 presents an intriguing opportunity. The company's focus on developing a novel ketamine analog with a potentially superior safety profile and efficacy could position them well in the competitive neuropsychiatric drug market.
The positive preclinical data, particularly the selective NMDA binding mechanism and favorable toxicology results, provide a strong foundation for MIRA's planned IND submission. If approved, this could significantly accelerate the company's timeline to potential commercialization.
However, investors should note that the path from preclinical success to FDA approval is long and often unpredictable. Many promising drug candidates fail in clinical trials and the neuropharmacology field is particularly challenging. MIRA's market capitalization and cash position will be important factors to watch, as the costs of clinical trials can be substantial.
If Ketamir-2 maintains its promising profile through human trials, it could potentially capture a significant share of the growing market for novel depression treatments. The global depression treatment market is projected to reach
Investors should closely monitor MIRA's progress with the IND submission and any subsequent updates on clinical trial designs and timelines. These will be key inflection points for the company's valuation and future prospects.
Latest positive preclinical data provides another step in the path to potential IND submission this year for novel ketamine analog
MIAMI, FL / ACCESSWIRE / July 25, 2024 / MIRA Pharmaceuticals, Inc. (NASDAQ:MIRA) ("MIRA" or the "Company"), a leading pre-clinical-stage pharmaceutical company, today announced new insights garnered from additional, recently received preclinical study data regarding the mechanism of action and toxicology data for its novel oral ketamine analog, Ketamir-2.
Ketamir-2 is MIRA's drug candidate being investigated as a potential treatment for neurological and neuropsychiatric disorders. The new preclinical study results announced today are the latest in a string of positive research developments which are progressing MIRA's goal of submitting an Investigational New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for Ketamir-2 later this year.
Mechanism of Action: Selective NMDA Inhibition
The latest preclinical data reveals that Ketamir-2 is a selective inhibitor of the NMDA receptor of glutamate, the primary excitatory neurotransmitter in the human brain, specifically interacting at the PCP-binding site of the NMDA complex. Ketamir-2 has a 30-50-fold lower affinity to the PCP site compared with ketamine. The lower affinity is important because at high affinity, compounds may affect neurobehavioral functions, potentially leading to side effects such as dissociation and hallucinations. Unlike traditional ketamine, which also affects several other sites on the NMDA receptor and interacts with opioid receptors, dopamine and serotonin transporters, and various acetylcholine receptors, Ketamir-2 exhibits unique selectivity and does not interact with these additional receptor sites. This selectivity is notable as it may contribute to a distinct pharmacological profile for Ketamir-2, potentially reducing the risk of side effects associated with these other interactions.
The potential benefits of Ketamir-2's selective binding also include:
1. Reduced Side Effects: By targeting only the NMDA receptor at the PCP-binding site, Ketamir-2 appears to avoid the broader spectrum of ketamine interactions with other receptors and transporters. This specificity may help minimize unwanted side effects, such as dissociation, hallucinations, and addictive potential, often observed with ketamine use.
2. Improved Safety Profile: The selective inhibition allows for a cleaner pharmacological profile, potentially leading to better tolerability and fewer adverse reactions in patients. These advantages could enhance patient compliance and overall treatment outcomes.
3. Enhanced Therapeutic Effectiveness: With a selective mechanism of action, Ketamir-2 could potentially deliver more consistent and predictable therapeutic effects, which may be particularly beneficial in treating conditions like depression, treatment-resistant depression (TRD), and post-traumatic stress disorder (PTSD).
Enhanced Safety Profile
Complementing its novel mechanism, recently conducted toxicology studies in rats and dogs have shown no toxicity at very high doses of Ketamir-2. These findings underscore Ketamir-2's excellent safety margin, further supported by its pronounced antidepressant and anxiolytic activities observed at oral doses five to tenfold lower than those tested in the toxicology studies. The substantial therapeutic window of Ketamir-2 offers promising potential for safe and effective use in human therapies.
Erez Aminov, Chairman & CEO of MIRA Pharmaceuticals, commented "During the course of this year, working with our research partners, we continue to discover and report on very promising attributes of Ketamir-2 that we hope will, collectively, enable our IND for this compound. These most recent insights into Ketamir-2's mechanism of action and safety profile mark a significant milestone in our preclinical development program. The novel selectivity and robust safety data bolster our confidence in Ketamir-2's potential as a transformative treatment for neurological and neuropsychiatric disorders. We are excited to advance this compound towards clinical trials, aiming to address the unmet needs of patients suffering from conditions such as depression, TRD and PTSD."
Dr. Itzchak Angel, Chief Scientific Advisor of MIRA Pharmaceuticals, added, "The ability of Ketamir-2 to selectively inhibit a single specific site at the NMDA receptor complex without affecting other sites is a remarkable finding. Combined with its strong safety profile and pronounced therapeutic effects, we believe that Ketamir-2 holds great promise as a groundbreaking treatment for mental health disorders. We look forward to continuing our IND enabling studies and our progression towards an IND for Ketamir-2."
Preclinical Progress and Future Plans
The additional data announced today builds on previous findings highlighting Ketamir-2's superior brain penetration and bioavailability. Unlike traditional ketamine, Ketamir-2 is not a substrate for P-glycoprotein (P-gp), a membrane protein that pumps drugs out of cells, including those in the brain. This characteristic may allow Ketamir-2 to penetrate the blood-brain barrier more effectively, enhancing its therapeutic potential.
If MIRA's IND is granted by the FDA, it would pave the way for human clinical trials, bringing Ketamir-2 one step closer to becoming a new standard of care for neurological and neuropsychiatric disorders.
About MIRA Pharmaceuticals
MIRA Pharmaceuticals, Inc. (NASDAQ: MIRA) is a pre-clinical-stage pharmaceutical development company with two neuroscience programs targeting a broad range of neurologic and neuropsychiatric disorders. MIRA holds the exclusive U.S., Canadian and Mexican rights for Ketamir-2, a novel, patent pending oral ketamine analog under investigation to potentially deliver ultra-rapid antidepressant effects, providing hope for individuals battling treatment-resistant depression, major depressive disorder with suicidal ideation and post-traumatic stress disorder. The U.S. Drug Enforcement Administration's scientific review of Ketamir-2 concluded that it would not be considered a controlled substance or listed chemical under the Controlled Substances Act and its governing regulations.
In addition, MIRA's novel oral pharmaceutical marijuana analog, MIRA-55, is currently under investigation for treating adult patients suffering from neuropathic pain as well as anxiety and cognitive decline, often associated with early-stage dementia. MIRA-55, if approved by the FDA, could mark a significant advancement in addressing various neuropsychiatric, inflammatory, and neurologic diseases and disorders. The U.S. Drug Enforcement Administration's scientific review of MIRA-55 concluded that it would not be considered a controlled substance or listed chemical under the Controlled Substances Act and its governing regulations. Additional information about the Company is available at: www.mirapharmaceuticals.com
Ketamir-2 and MIRA-55 are in early-stage preclinical development. There is no assurance that the products will proceed through development or will receive FDA approval for marketing.
Cautionary Note Regarding Forward-Looking Statements
This press release and the statements of the Company's management related thereto contains "forward-looking statements," which are statements other than historical facts made pursuant to the safe harbor provisions of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. These statements may be identified by words such as "aims," "anticipates," "believes," "could," "estimates," "expects," "forecasts," "goal," "intends," "may," "plans," "possible," "potential," "seeks," "will," and variations of these words or similar expressions that are intended to identify forward-looking statements. Any statements in this press release that are not historical facts may be deemed forward-looking. These forward-looking statements include, without limitation, statements regarding the anticipated benefits of the study results described herein as well as the timing for the Company's other preclinical studies and the filing of an IND for Ketamir-2. Any forward-looking statements in this press release are based on the Company's current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties (many of which are beyond the Company's control) that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These and other risks concerning the Company's programs and operations are described in additional detail in Annual Report on Form 10-K for the year ended December 31, 2023 and other SEC filings, which are on file with the SEC at www.sec.gov and the Company's website at https://www.mirapharmaceuticals.com/investors/sec-filings. The Company explicitly disclaims any obligation to update any forward-looking statements except to the extent required by law.
Contact Information
Erez Aminov
Chairman & Chief Executive Officer
info@mirapharma.com
(786) 432-9792
SOURCE: MIRA Pharmaceuticals, Inc.
View the original press release on accesswire.com
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