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Aptiganel (originally CNS-1102, later tested under the name Cerestat) was one of the most closely watched NMDA-antagonist neuroprotectants of the 1990s, developed by Cambridge NeuroScience to fight acute ischemic stroke. The logic was straightforward and, at the time, compelling: strokes trigger a flood of glutamate that overactivates NMDA receptors and kills neurons through excitotoxicity, so blocking the channel early should limit the damage. It reached large Phase III trials, but the pivotal study (published in JAMA in 2001) was stopped for futility, showing no benefit over placebo while producing hallucinations, agitation, and blood pressure spikes at the doses needed for neuroprotection. Aptiganel became one of the signature failures cited in the broader post-mortem on why NMDA-antagonist neuroprotection never worked clinically for stroke, despite decades of strong animal data.
- strong preclinical neuroprotective data in ischemia models
- clear proof-of-mechanism for NMDA-driven excitotoxicity
- hallucinations and psychotomimetic effects at effective doses
- hypertension
- Aptiganel's failure is one of the most frequently cited examples in reviews explaining why the entire NMDA-antagonist neuroprotectant class collapsed for stroke, despite dozens of drugs and decades of promising animal research.
- It shares its core mechanism, non-competitive channel block, with PCP and ketamine, but was never studied or used recreationally; its whole development arc lived inside stroke units and clinical trials.
Mechanism
Non-competitive, high-affinity channel blocker, pharmacologically related to PCP and MK-801, intended to block excitotoxic calcium influx following acute .
Safetyrisks and cautions, not medical advice
This is one of the few stopped trials where the drug looked actively harmful rather than merely useless. In the pivotal stroke study of 628 patients the sponsor and the independent safety board halted enrolment for futility and a mortality imbalance: 26.3 percent of the high-dose group had died by 120 days against 19.2 percent on placebo, and neurological scores at seven days were slightly worse on drug than on saline. The doses needed for neuroprotection also produced hypertension, sedation, confusion and hallucinations, with catatonia at the top of the range.
History
Developed by Cambridge NeuroScience in the early-to-mid 1990s; advanced into Phase III acute ischemic stroke trials; the pivotal trial (Albers et al, 2001, JAMA) was halted for futility and safety concerns, and the program was discontinued.
Subjective profileweighing the evidence above
A textbook case of neuroprotection that worked beautifully in rodents and fell apart in humans, part of a graveyard of roughly thirty failed NMDA-antagonist stroke drugs.
Resources
This entry is here for reference.
Research
- 1.Aptiganel hydrochloride in acute ischemic stroke: a randomized controlled trial
- 2.Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury?
2 listed here; entry last updated July 2026
Reviews
My notesprivate to this device
FAQ
Did aptiganel ever help stroke patients?
No. Its pivotal Phase III trial was stopped early because an interim analysis showed no benefit over placebo, while patients experienced hallucinations and blood pressure spikes.
Why did so many NMDA-antagonist stroke drugs fail around the same time?
A widely cited 2002 review noted that the doses needed to block enough NMDA receptors for neuroprotection also caused unacceptable psychotomimetic and cardiovascular side effects, and the treatment window in real stroke patients was likely much narrower than in animal models.
Limitations of the evidence
- no demonstrated clinical benefit over placebo
Adverse effects
- hallucinations and psychotomimetic effects at effective doses
- hypertension
Notes and cautions
- trial halted early for futility