Merck

Last updated January 31, 2026

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Spiropiperidine nicotinic allosteric modulators: MerckRecent Research Landscape

Off-target binding and rapid receptor desensitization limit the efficacy of traditional nicotinic agonists. These innovations utilize spiropiperidine scaffolds to target specific allosteric sites for precise neuroreceptor signaling control.

What technical problems is Merck addressing in Spiropiperidine nicotinic allosteric modulators?

Insufficient receptor subtype selectivity

(4)evidences

Insufficient cholinergic signaling in the central nervous system. Restoring receptor sensitivity improves synaptic plasticity and memory processing.

Insufficient receptor subtype selectivity

(2)evidences

Off-target binding at other muscarinic subtypes causes severe side effects. Achieving subtype-specific modulation prevents adverse systemic toxicity.