Harmaline induced Tremor Model Development Service

Are you currently facing long drug development cycles, challenges in identifying effective anti-tremor compounds, or difficulties in validating preclinical models for movement disorders? Our harmaline-induced tremor model service helps you accelerate drug discovery and obtain high-quality, translatable data through advanced pharmacological and neurophysiological assessment techniques.

The harmaline-induced tremor model is a well-established and highly valuable preclinical tool for studying neurological tremors, particularly Essential Tremor (ET). This model leverages the tremorgenic properties of harmaline, a β-carboline alkaloid, to induce a reproducible action tremor in rodents. Its utility stems from its ability to mimic key aspects of human tremor pathophysiology, primarily through its selective activation of the inferior olivary nucleus and its impact on the olivocerebellar circuit. This makes it an indispensable asset for screening novel anti-tremor compounds and elucidating their mechanisms of action.

How Our Harmaline-Induced Tremor Models Can Assist Your Project?

Creative Biolabs' harmaline-induced tremor model service provides a robust and reliable platform for evaluating the efficacy and mechanism of action of novel anti-tremor compounds. Clients can expect specific deliverables including comprehensive efficacy data, detailed mechanistic insights, and a clear understanding of their compound's potential in a highly translatable preclinical setting. We deliver actionable intelligence to de-risk your drug development pipeline.

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Workflow

Our streamlined workflow ensures precise and reproducible results, designed for seamless integration into your drug discovery program, and is suitable for visualization as a flowchart:

• Required Starting Materials:

To initiate a study, clients typically provide:

1. Test Article (Compound): Detailed information on the compound's chemical structure, purity, solubility, and recommended dosing regimen.
2. Study Design Parameters: Specific objectives, desired animal species (e.g., mouse, rat, guinea pig), number of treatment groups, and any specific readouts or endpoints.
3. Safety Data: Preliminary toxicology or safety data to inform appropriate dosing ranges and ensure animal welfare.

• Final Deliverables:

Upon completion of the service, you will receive:

1. Detailed Study Report: A comprehensive document outlining methods, results, statistical analyses, and conclusions.
2. Raw Data Files: All raw data from tremor quantification methods, ensuring full transparency and allowing for independent analysis.
3. Scientific Presentation/Consultation: An optional presentation of findings and a consultation with our scientific team to discuss implications and future directions.

• Estimated Timeframe:

The typical timeframe for a harmaline-induced tremor study ranges from 3 to 6 weeks, depending on the complexity of the study design, the number of compounds to be tested, and the specific endpoints required. Expedited timelines can be discussed for urgent projects.

Why Choose Us?

CBL stands at the forefront of neurological preclinical research, offering unparalleled expertise and a commitment to scientific excellence in harmaline-induced tremor models. Our two decades of experience translate into robust, reliable, and highly translatable data that truly accelerates your drug discovery. We combine deep scientific understanding with cutting-edge technology to provide a service that is both efficient and insightful.

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Customer Reviews

[Precise Efficacy Data] Using CBL's harmaline-induced tremor model in our research has significantly improved our ability to obtain precise, quantitative efficacy data for our novel compounds. The force plate actimetry provided an unparalleled level of detail compared to our previous methods, allowing us to confidently differentiate subtle compound effects. — 2024, Dr. L*a Smith

[Accelerated Screening] CBL's harmaline-induced tremor model service has greatly facilitated our high-throughput screening efforts. The acute, single-day procedure meant we could evaluate a large number of test articles efficiently, dramatically reducing our screening cycle time. Their team's expertise in protocol optimization was invaluable. — 2023, Dr. J*n Doe

[Mechanistic Insights] The detailed neurophysiological readouts from CBL's harmaline-induced tremor model provided crucial mechanistic insights into our compound's action on the olivocerebellar circuit. This deeper understanding allowed us to refine our lead compounds with greater precision, a critical advantage over simpler behavioral models. — 2024, Dr. M*k Brown

Harmaline-Induced Tremor Models

The harmaline-induced tremor model in rodents (typically mice, rats, and guinea pigs) has been a cornerstone of tremor research for decades, offering a highly reproducible and pharmacologically sensitive platform. Harmaline, a naturally occurring beta-carboline alkaloid, induces a characteristic action tremor, typically in the 10-16 Hz range, that shares significant similarities with human tremors, particularly essential tremor and the action component of Parkinsonian tremor.

Mechanism of Action:

Harmaline's tremorgenic effect is primarily mediated through its selective activation of neurons within the inferior olivary nucleus (ION) in the brainstem. This activation leads to:

• Increased Firing Rate of ION Neurons: Harmaline causes a rhythmic, synchronous burst firing of ION neurons, altering their electrical coupling.
• Propagation to the Cerebellum: The ION projects to the cerebellar cortex via climbing fibers, driving Purkinje cell (PC) activity. The deep cerebellar nuclei (CN) are also critical for tremor expression. This generates coherent oscillatory activity in PCs and rhythmic activity in CN neurons. Studies have shown that while CN neurons normally display coherent oscillations during voluntary movements, harmaline disrupts this coherence, leading to a loss of coherence in neuronal pairs.
• Disruption of Cerebellar-Thalamic-Cortical Circuit: The rhythmic cerebellar output, relayed through the thalamus to the motor cortex, results in the characteristic 8-12 Hz tremor.

Fig.1 Suppression of the harmaline-induced body tremor by NNC was not accompanied by restoration of firing pattern properties of single CN neurons.¹

What We Can Offer

At CBL, our harmaline-induced tremor models service is designed to provide comprehensive and flexible solutions tailored to the unique needs of your neurological drug discovery program. We are committed to delivering high-quality, translatable data that drives your project forward.

• Customized Study Design: We offer highly flexible and customized study designs, adapting protocols for animal species, dosing regimens, and specific tremor quantification methods to precisely match your research objectives.
• Comprehensive Tremor Assessment: Utilize a range of advanced tremor quantification techniques, including Electromyography (EMG), Accelerometry, and Force Plate Actimetry, ensuring the most accurate and detailed data on tremor severity, frequency, and amplitude.
• Expert Protocol Optimization: Benefit from our extensive experience in optimizing harmaline administration and experimental conditions to ensure consistent tremor induction and maximize the reproducibility of your results.
• Efficient Acute Screening: Leverage the acute nature of the harmaline model for rapid and cost-effective screening of numerous compounds, significantly accelerating your early-stage drug discovery efforts.
• Mechanistic Insights: Gain a deeper understanding of your compound's mechanism of action through detailed analysis of its impact on the olivocerebellar circuit and related neurophysiological pathways.
• Dedicated Scientific Support: Partner with our team of neurobiology experts who provide scientific consultation, data interpretation, and strategic guidance throughout your project, from initial design to final report.
• Robust Quality Assurance: All studies are conducted under stringent quality control measures and ethical guidelines, ensuring the integrity and reliability of your data for regulatory submissions and publications.

Related Services

Beyond our core harmaline-induced tremor model, CBL offers a suite of complementary services designed to provide a holistic approach to your neurological drug discovery programs:

• Neuroinflammation Assays
• Neurodegenerative Disease Models
• Biomarker Discovery & Validation
• Histology & Pathology Services

Ready to advance your anti-tremor compound? Contact our expert team today to discuss your specific research needs and discover how we can help you achieve your preclinical milestones efficiently and effectively.

Contact Our Team for More Information and to Discuss Your Project.

Reference

1. Baumel, Yuval et al. "Chemical suppression of harmaline-induced body tremor yields recovery of pairwise neuronal coherence in cerebellar nuclei neurons." Frontiers in systems neuroscience vol. 17 1135799. 11 May. 2023, doi:10.3389/fnsys.2023.1135799. Distributed under Open Access license CC BY 4.0, without modification.