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Cilomilast (Ariflo) is a second-generation oral selective PDE4 inhibitor developed by GlaxoSmithKline for COPD and asthma. It reached FDA review but was rejected in 2003-2004 because the respiratory benefit was small and gastrointestinal side effects were dose-limiting. It is not approved anywhere. There is essentially no human cognition data; a single 2025 mouse study reported that cilomilast reversed scopolamine-induced memory deficits through the cAMP/PKA-CREB-BDNF pathway.
- Modest but genuine bronchodilation/anti-inflammatory effect in COPD (trough FEV1 ~+40 mL)
- Well-characterized oral pan-PDE4 pharmacology
- Reduced amyloid-beta and neuroinflammation in a single rodent model
- Nausea, vomiting, diarrhea, abdominal pain, dyspepsia (early)
- Headache
- Weight loss and psychiatric signals (PDE4 class)
- Higher study withdrawal than placebo
- Cilomilast was one of the first oral PDE4 inhibitors to reach FDA review for COPD; and its rejection helped push the field toward better-tolerated successors.
- Its only memory data come from a single 2025 mouse study; there are no human cognition trials.
- The gastrointestinal side effects that sank it are the same class effect seen across oral PDE4 inhibitors.
Mechanism
Pan-PDE4 inhibitor (A/B/C/D) that raises , activating PKA and and increasing , alongside broad anti-inflammatory action. Its pronounced emetogenicity is consistent with PDE4D engagement (subtype selectivity is literature-reported, not independently binding-verified here).
receptor fingerprint
PDE4 (pan A/B/C/D)Inhibits
Airway inflammationSuppresses
/PKA/ pathwayElevates
Upregulates
Evidencehow good the literature is
Human RCTs (COPD): trough FEV1 improved by roughly 40 mL versus placebo over 24 weeks, and a Cochrane meta-analysis confirms a small, borderline class effect with more GI adverse events. Rodent (cognition): one 2025 study showed scopolamine-memory reversal with reduced amyloid-beta and neuroinflammation. No human cognition trials exist.
Dosingtypical ranges, not medical advice
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Safetyrisks and cautions, not medical advice
Oral PDE4 class toxicity: nausea, vomiting, diarrhea, abdominal pain, dyspepsia (mostly early) and headache. GI effects interfered with daily activity in roughly 17% versus 8% on placebo, with class weight-loss and psychiatric signals and higher study withdrawal than placebo. It is not approved anywhere and is not a supplement.
History
Developed by GlaxoSmithKline as a follow-on to first-generation PDE4 inhibitors, cilomilast was submitted for COPD but rejected at FDA review in 2003-2004 over a modest efficacy-to-tolerability balance. Development did not continue.
Reputation
Known in the PDE4 field as a cautionary example of the class's narrow therapeutic window; real anti-inflammatory activity undone by dose-limiting GI effects. The lone rodent cognition paper is a curiosity, not a basis for human nootropic use.
Subjective profileweighing the evidence above
A real but failed oral PDE4 drug. Its respiratory effect is genuine yet modest, and the only cognition signal is a single rodent study; mechanistically interesting for PDE4-class completeness, weak as a human nootropic.
Resources
This entry is here for reference.
Research
- 2001first citedCilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic ob…
- 2020meta-analysisPhosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.
- 2025most recentNeuroprotective Effects of Cilomilast and Chlorogenic Acid Against Scopolamine-Induced Memory D…
- 1.Neuroprotective Effects of Cilomilast and Chlorogenic Acid Against Scopolamine-Induced Memory Deficits via Modulation of the cAMP/PKA-CREB-BDNF Pathway.
- 2.Cilomilast for COPD: results of a 6-month, placebo-controlled study of a potent, selective inhibitor of phosphodiesterase 4.
- 3.Cilomilast, a selective phosphodiesterase-4 inhibitor for treatment of patients with chronic obstructive pulmonary disease: a randomised, dose-ranging study.
- 4.Phosphodiesterase-4 inhibitors for chronic obstructive pulmonary disease.
4 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
Is cilomilast a nootropic?
No. It is a failed COPD drug with only a single rodent memory study; there is no human cognition evidence, and it is not approved for any use.
Why was it never approved?
The FDA rejected it in 2003-2004 because the respiratory benefit was small and gastrointestinal side effects were dose-limiting.
Can I buy it?
No. It is an unapproved investigational compound, not a marketed medicine or supplement.
Adverse effects
- Nausea, vomiting, diarrhea, abdominal pain, dyspepsia (early)
- Headache
- Weight loss and psychiatric signals (PDE4 class)
- Higher study withdrawal than placebo