Over the last 2 decades, work from multiple laboratories has established that L-type calcium channels (LTCCs) are critical mediators of experience-dependent plasticity in the brain. More recently, these channels have been identified to be key for various neuronal processes that are essential for normal brain development, connectivity, and function. Focusing on novel psychotropic target discovery and subsequent development for years, Creative Biolabs has established an advanced technology platform with a mature development system to provide reliable services to global researchers.
Introduction to LTCC blockers
LTCCs exert fundamental physiologic effects in several organ systems, particularly the heart and smooth muscles of the intestine and vasculature. These channels are also widely expressed in the central nervous system (CNS) and have been shown to influence neurotransmitter release, neuron excitability, learning, memory, and other physiologic functions. Ten calcium-channel blockers are currently approved for clinical use in the United States. These 10 drugs belong to four different chemical classes: phenylalkylamines (verapamil), benzothiazepines (diltiazem), DHPs (nifedipine, amlodipine, felodipine, isradipine, nicardipine, nisoldipine, and nimodipine), and diarylaminopropylamines (bepridil). All calcium-channel antagonists reduce Ca2+ flux by binding to the α1 subunit of the LTCC and thus pharmacologically affecting muscle contraction, vasodilatation, hormone release, neurotransmitter release, neuronal plasticity, and more.
Targeting L-Type Calcium Channels in the Treatment of Neuropsychiatric Disorders and Drug Dependence
The efficacy of the LTCC blocker verapamil in alleviating acute mania observed in BD has been explored in several studies. When verapamil was administered in combination with the mood stabilizer lithium to patients with BD who were unresponsive to lithium or in conjunction with the antipsychotic medication chlorpromazine, there was a significant improvement in manic symptoms. This suggests that verapamil could have some potential for maintenance therapy of mania.
Verapamil has also been tested in patients with SCZ. In patients with acute SCZ, verapamil treatment when administered as a monotherapy resulted in a significant decrease in psychotic symptoms. These findings were confirmed in a separate study that reported a similarly small, but significant, attenuation of psychotic symptoms with verapamil.
Evidence from rodent studies has identified an important role of LTCCs in multiple aspects of cocaine addiction, making these channels a potential target for the treatment of addiction. A recent study reported enhanced subjective effects with isradipine. The effects of LTCCs have also been tested on cocaine craving, the primary cause of relapse to cocaine use, with nimodipine, amlodipine, and isradipine reducing cocaine craving.
The impacts of LTCC blockers on the subjective effects of morphine are mixed. While one study reported a reduction in the subjective effect of morphine with verapamil, another study showed no influence of nimodipine, verapamil, and diltiazem on counteracting morphine's subjective effects in healthy humans. Separately, it has been reported that nifedipine treatment caused confusion in individuals that were in morphine withdrawal. These studies suggest that LTCC blockers may show selective effects in morphine-dependent individuals, having beneficial effects in some but detrimental effects in others.
Services at Creative Biolabs
Having been committed to psychotropic drug development for years, Creative Biolabs has accumulated extensive experience from hundreds of successful projects and thus provides reliable target development services. The advanced technology platform and mature development system will assure the high quality of every step during the drug development process. Meanwhile, our Ph.D. level scientists will help with any question our customers meet during the services.
Advantages
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Reliable: Hundreds of successful precedents
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Flexible: Either stand-alone services or integrated projects are both welcomed
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Professional: Advanced technology with Ph.D. level experts
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Top-rated customer experience: Efficient and cost-effective services
LTCC blockers have been shown to be important in psychotropic drug development. Focusing on the application of LTCC blockers in psychiatric disorders, Creative Biolabs provides global researchers with high-quality relative target development services. We aspire to promote industry development through our services. If you have any other questions, please contact us for more information.
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