Description

Product Description

L-659837 is a potent and selective neurokinin 2 (NK2) receptor antagonist widely used in studies of smooth muscle contraction, bladder physiology, and tachykinin-mediated signaling. The neurokinin receptor family, including NK1, NK2, and NK3 subtypes, plays a crucial role in mediating various physiological and pathophysiological responses, such as pain transmission, airway constriction, and urinary tract contractility.

By selectively antagonizing the NK2 receptor, L-659837 provides researchers with a valuable pharmacological tool to study the effects of substance P and neurokinin A in regulating muscle tone and organ function.

Structural and Biochemical Properties

L-659837 is a small-molecule compound designed to competitively inhibit NK2 receptor activation by endogenous tachykinins. It exhibits high affinity for the receptor, effectively blocking neurokinin A binding and preventing subsequent intracellular calcium mobilization. This results in attenuation of smooth muscle contraction in tissues such as the urinary bladder, gastrointestinal tract, and airways.

The compound’s chemical stability and receptor selectivity make it ideal for both in vitro and in vivo pharmacological studies. Researchers often use L-659837 as a benchmark antagonist to evaluate new NK2 receptor modulators or to dissect complex tachykinin signaling networks.

Physiological and Research Relevance

The NK2 receptor, a member of the G-protein–coupled receptor (GPCR) family, is prominently expressed in smooth muscle cells, including those of the urinary bladder and respiratory system. Activation of this receptor by neurokinin A induces muscle contraction via the Gq/PLC/IP3 pathway, leading to calcium release from intracellular stores. L-659837 effectively interrupts this signaling cascade by occupying the receptor’s binding site, thereby preventing contraction and restoring baseline muscle tone.

This pharmacological mechanism makes L-659837 highly valuable in:

• Urology research, including studies of detrusor overactivity and bladder hyperreflexia.

• Smooth muscle physiology, investigating tachykinin-mediated signaling pathways.

• Drug discovery, serving as a reference antagonist in screening NK2-targeting compounds.

By providing controlled inhibition of NK2 receptors, L-659837 supports investigations into the pathophysiology of bladder disorders such as overactive bladder (OAB), interstitial cystitis, and urinary urgency.

Product Specifications

Mechanism of Action

L-659837 functions as a competitive antagonist at the NK2 receptor, a GPCR primarily activated by neurokinin A. Upon ligand binding, the NK2 receptor typically triggers Gq/11-mediated activation of phospholipase C, resulting in IP3 generation and calcium release. These intracellular calcium surges activate contractile proteins, promoting smooth muscle contraction.

L-659837 binds to the receptor’s orthosteric site without inducing receptor activation, effectively preventing neurokinin A from initiating downstream signaling. The result is a marked reduction in calcium-dependent contractility in smooth muscle tissues, particularly those of the urinary bladder and airway systems.

In experimental settings, the compound has been shown to inhibit GR64349-induced contraction, validating its role as a reliable NK2 receptor blocker. L-659837 does not significantly affect NK1 or NK3 receptor subtypes, confirming its high selectivity and suitability for receptor-specific investigations.

Side Effects

L-659837 is intended strictly for in vitro and in vivo research applications. Reported experimental observations include:

• Transient reduction in muscle responsiveness during long-term exposure.

• Minimal cross-reactivity with NK1 or NK3 receptors at research concentrations.

• No cytotoxicity in standard cell culture models when properly dosed.

As with all pharmacological agents, laboratory personnel should follow appropriate safety and handling protocols. Avoid inhalation, ingestion, or direct contact.

Keywords

L-659837, CAS 125989-10-8, NK2 receptor antagonist, neurokinin A inhibitor, smooth muscle pharmacology, bladder research compound, tachykinin pathway blocker, GPCR ligand, urinary dysfunction studies, receptor selectivity analysis

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