5-HT Assays

If you aim to improve the translatability of your drug discovery research, human tissue testing is an invaluable tool. It allows you to gather human data before clinical trials, offering insights into drug responses and off-target effects on cardiovascular tissues. At REPROCELL, our scientists specialize in testing the effects of compounds on human blood vessels, providing a critical bridge between preclinical and clinical research phases. You can find examples of our work listed below.

Understanding the Role of 5-HT2A Receptors in Cardiovascular Drug Development

The 5-HT_2A receptor, a Gq-coupled protein receptor (GPCR), plays a significant role in the cardiovascular system (CVS), in addition to its expression in other tissues like the brain and gut. Within the CVS, 5-HT_2A receptors are expressed by key cell types such as platelets, endothelial cells, and smooth muscle cells. These receptors are integral to maintaining vascular function, particularly in processes such as inflammation, wound healing, and vascular tone regulation.

When activated by 5-HT (serotonin), 5-HT_2A receptors mediate critical cardiovascular responses including platelet aggregation and vasoconstriction. These functions are essential during wound healing, where rapid clot formation and vascular repair are required. The receptor’s influence on vasoconstriction also highlights its role in controlling blood flow and pressure, making it a crucial target for investigating drug-induced vascular effects.

In cardiovascular drug development, understanding the interaction between new compounds and 5-HT_2A receptors is vital. Off-target effects on these receptors could lead to unintended cardiovascular outcomes, making it essential to assess their impact early in the drug discovery process. At REPROCELL, our assays are designed to evaluate the effects of compounds on human blood vessels, enabling you to predict and mitigate potential cardiovascular risks.

5-HT_1B Receptors: Multifaceted Roles in Neurology and Vascular Function

Primarily located in central nervous and vascular tissues, the 5-HT_1B receptor influences numerous neurological, physiological, and pathological processes. It plays a role in addiction, migraine, and sleep regulation due to its control over various neurotransmitters. The 5-HT_1B receptor is also linked to mood, memory, aggression, stress sensibility, and anxiety, with notable presence in the brain's "extended amygdala," a reward circuit associated with drug reinforcement. Genetic variations in 5-HT_1B are associated with addiction and OCD in humans.

In the cardiovascular system, the 5-HT_1B receptor is concentrated in cerebral arteries, where its activation induces vasoconstriction, an effect that is beneficial in the treatment of migraine, to counteract excessive vasodilatation. A notable example is the 5-HT_1B agonist and common treatment for migraine, sumatriptan. During initial human trials, cardiac events were reported in a small number of patients following intravenous administration. In vitro studies in human isolated cerebral and coronary arteries became important in clarifying the therapeutic window for 5-HT_1B/1D agonists such as sumatriptan, helping to determine the safety margin between contraction of cerebral arteries (to reduce the symptoms of migraine) and undesirable vasoconstriction of coronary arteries. This allowed clinical trials to proceed, and today sumatriptan is considered safe for migraine treatment in patients without cardiovascular contraindications. Since the launch of sumatriptan, other triptans available for treating migraine by targeting the 5-HT_1B receptor include almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and zolmitriptan.

Explore Our Assay Catalog or Customize Your Research Solution

At REPROCELL, we offer a comprehensive range of assays to evaluate the effects of your compound on human tissues. You can explore examples of our work in our assay catalog or contact us to arrange a custom solution tailored to your research needs. Leverage our expertise to enhance the predictability and safety of your drug discovery projects.