Olcegepant
Also known as: BIBN 4096 BS, BIBN4096BS, BIBR 1532, CGRP antagonist, Olcegepant
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Summary
Olcegepant is an investigational small‑molecule peptide‑mimetic that blocks the calcitonin gene‑related peptide (CGRP) receptor. Developed for acute migraine treatment, it is administered intravenously in research settings. Early clinical trials and a network meta‑analysis have shown it to be highly effective at relieving migraine pain within two hours, positioning it among the most potent CGRP antagonists studied to date.
Mechanism of Action
Olcegepant binds to the CGRP receptor complex, preventing the endogenous peptide CGRP from activating the receptor on trigeminal and vascular cells. By inhibiting CGRP‑mediated vasodilation and nociceptive signalling, the drug reduces neurogenic inflammation and the pain cascade that underlies migraine attacks. Its peptidomimetic structure enables high affinity for the receptor despite being a small molecule.
What the Research Shows
Pre‑clinical work identified CGRP as a key migraine mediator, and olcegepant was the first intravenously administered CGRP‑receptor antagonist shown to terminate migraine attacks in humans (2004). A 2019 network meta‑analysis of ten randomized trials (8,174 participants) reported an odds ratio of 4.09 for 2‑hour pain relief versus placebo, ranking it as the most effective of six gepants evaluated. Subsequent reviews cite its efficacy but note that development was halted because of formulation challenges and safety concerns, leaving olcegepant in the investigational stage.
Reported Benefits
Evidence from randomized trials indicates that olcegepant provides rapid and substantial migraine pain relief, outperforming placebo and several other CGRP antagonists. Its mechanism targets a pathway directly implicated in migraine pathophysiology, making it a potential option for patients who cannot use triptans or who have contraindications to other acute therapies.
Limitations of the Evidence
Olcegepant has never received regulatory approval and is only available for intravenous use in research protocols. Data on long‑term safety, optimal dosing, and comparative effectiveness are limited. Development was discontinued partly due to lack of oral formulation and concerns about hepatotoxicity observed with earlier gepants, leaving gaps in the evidence base.
Safety Considerations
Adverse‑event reporting for olcegepant is sparse; the network meta‑analysis did not identify a significant increase in toxicity versus placebo, but the overall safety profile remains incompletely characterised. Earlier first‑generation gepants raised concerns about liver enzyme elevations, prompting caution. Until more robust safety data are available, olcegepant should be considered experimental and used only under controlled clinical conditions.
How It Is Administered
Olcegepant is formulated for intravenous infusion. No oral or alternative routes have been established for clinical use. In research settings, it is administered as a single IV dose during an acute migraine attack.
Routes of Administration
Goals & Uses
- Acute migraine treatmentNeurology / PainModerate
- Cluster headacheNeurology / PainLow
- Acute migraine reliefAnalgesicModerate
- CGRP pathway proof-of-conceptResearchHigh
Contraindications
- Severe hepatic impairmentOrganModerateLiver function concerns
- Severe cardiovascular diseaseCardiovascularModerate
- Hypersensitivity to olcegepant or excipientsAllergyHigh
- Known hypersensitivity to olcegepantAllergyHigh
Adverse Effects
- HypotensionCardiovascularUncommonLow blood pressure
- FlushingVascularCommonWarmth and redness of the skin
- NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
- ParesthesiaNeurologicUncommonTingling or numbness sensation
- DizzinessNeurologicUncommonFeeling faint, lightheaded, or unsteady
- Infusion-site reactionsLocal / AdministrationUncommon
Drug Interactions
- Triptans (e.g., sumatriptan)Moderate
- TriptansLow
- CYP3A4 inhibitorsLow
Population Constraints
- PregnancyReproductive SafetyRelative
- Renal impairmentOrgan ImpairmentRelative
- Pediatric patientsAgeRelative
- Pediatric patients (<18 y)AgeAbsolute
- Pregnant or lactating womenReproductiveRelative
Regulatory Status
- European UnionInvestigationalNot authorized by EMA
- United StatesInvestigationalNo FDA approval; clinical trial use only
- United KingdomInvestigationalNot licensed by MHRA
Development discontinued; not approved in US, EU, or UK. Investigational use only in clinical trials.
Evidence & Sources
- Journal ArticleModerateAggarwal M, Puri V, Puri S2012-01-01T00:00:00.000000Z
- Journal ArticleHighXu F, Sun W2019-01-01T00:00:00.000000Z
- Journal ArticleHighArgyriou AA, et al.2022-01-01T00:00:00.000000Z
- Journal ArticleModerateYounis S, et al.2024-01-01T00:00:00.000000Z
- Journal ArticleModerateTepper SJ2018-01-01T00:00:00.000000Z
- Journal ArticleModerateBenemei S, et al.2009-01-01T00:00:00.000000Z
Frequently Asked Questions
How does olcegepant differ from triptans?
Triptans act on serotonin (5‑HT1B/1D) receptors to cause vasoconstriction, whereas olcegepant blocks the CGRP receptor, preventing peptide‑mediated vasodilation and pain signalling without directly affecting serotonin pathways.
Is olcegepant approved for migraine treatment?
No. Olcegepant remains an investigational drug used only in clinical research; it has not obtained regulatory approval for any indication.
What route of administration is used for olcegepant?
The compound is delivered intravenously. No oral or other formulations have been developed for routine clinical use.
What are the known side effects of olcegepant?
Published trials provide limited adverse‑event data; no major safety signals were reported in the meta‑analysis, but earlier gepants raised concerns about liver toxicity, so safety remains an area of active investigation.
Who might benefit from olcegepant?
Patients with acute migraine who cannot take triptans or have contraindications may potentially benefit, but its use is currently restricted to research contexts pending further efficacy and safety data.
What is Olcegepant?
Olcegepant is an investigational small‑molecule peptide‑mimetic that blocks the calcitonin gene‑related peptide (CGRP) receptor. Developed for acute migraine treatment, it is administered intravenously in research settings. Early clinical trials and a network meta‑analysis have shown it to be highly effective at relieving migraine pain within two hours, positioning it among the most potent CGRP antagonists studied to date.
What is Olcegepant used for?
Olcegepant is educationally associated with: Acute migraine treatment, Cluster headache, Acute migraine relief, CGRP pathway proof-of-concept. Educational only — not medical advice.
How is Olcegepant administered?
Recorded routes of administration: Intravenous.
What are the potential side effects of Olcegepant?
Reported adverse effects include: Hypotension, Flushing, Nausea, Paresthesia, Dizziness, Infusion-site reactions. This list is not exhaustive — consult a qualified clinician.
Who should avoid Olcegepant?
Recorded contraindications: Severe hepatic impairment, Severe cardiovascular disease, Hypersensitivity to olcegepant or excipients, Known hypersensitivity to olcegepant. Consult a qualified clinician before use.