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NGX267 started life at Neurogen Corporation and was carried forward by TorreyPines Therapeutics in the mid-to-late 2000s as a dual M1/M4 muscarinic agonist with two proposed uses: improving cognition in Alzheimer's disease and treating xerostomia (severe dry mouth), a side effect common in Sjogren's syndrome and antipsychotic treatment. Its first-in-human dose-escalation study, published in 2009, used an adaptive statistical design that ended up getting cited almost as often for its methodology as for the drug itself. TorreyPines' broader pipeline stalled soon after, the company dissolved and merged into Raptor Pharmaceutical around 2009-2010, and NGX267 was left without a sponsor to carry it into later-phase trials.
- dual M1/M4 mechanism aimed at both cognition and dry-mouth relief
- completed a published first-in-human dose-escalation study
- adaptive trial design considered methodologically notable in its own right
- cholinergic side effects typical of muscarinic agonists at higher doses
- NGX267's first-in-human trial doubled as a statistics paper about adaptive dose-escalation design; it is cited nearly as often for its trial methodology as for the drug's own pharmacology.
Mechanism
NGX267 is a dual M1/M4 receptor , intended to enhance central cognitive circuits while also stimulating peripheral M3-adjacent salivary gland function for dry-mouth indications.
Safetyrisks and cautions, not medical advice
NGX267's only detailed human study was built to find the dose at which people start having problems. The first-in-man design defined its ceiling by a weighted count of moderate and severe adverse events and then deliberately concentrated dosing near that ceiling, which is an efficient way to map tolerability and a poor way to reassure anyone about ordinary doses. The specific events were never published. A later 24-patient crossover trial in dry mouth from Sjogren's syndrome finished without posted results. Muscarinic agonists slow the heart and turn the gut and salivary glands up, which is the likely shape of that ceiling.
History
Originated at Neurogen Corporation, advanced by TorreyPines Therapeutics through a first-in-human Phase I dose-escalation trial (published 2009); development stalled after TorreyPines dissolved and merged into Raptor Pharmaceutical around 2009-2010.
Resources
This entry is here for reference.
Research
1 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Why was NGX267 tested for both Alzheimer's and dry mouth?
Its dual M1/M4 muscarinic activity was thought to help central cognitive circuits (M1) and peripheral salivary gland output (M4-adjacent signaling), giving it two distinct potential indications from one mechanism.
What happened to NGX267's developer?
TorreyPines Therapeutics, which had taken over the compound from Neurogen Corporation, dissolved and merged into Raptor Pharmaceutical around 2009-2010, and NGX267 did not find a new sponsor to continue its development.
Limitations of the evidence
- no completed efficacy trial for either proposed indication; development halted early
Adverse effects
- cholinergic side effects typical of muscarinic agonists at higher doses