Sincalide
Gut Health / DiagnosticAlso known as: Kinevac
Mechanism
A synthetic version of the active part of cholecystokinin (CCK), the hormone that makes your gallbladder contract after a fatty meal. Used in medical imaging to stimulate gallbladder contraction so doctors can measure the ejection fraction (how well the gallbladder empties) — a key test for diagnosing gallbladder dysfunction. Also used to speed up barium transit during GI X-ray studies.
Technical detail
Synthetic C-terminal octapeptide of cholecystokinin (CCK-8): Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2. Contains the sulfated tyrosine critical for CCK-A receptor (CCK1R) selectivity. Binds CCK1R (Gq-coupled GPCR) on gallbladder smooth muscle: PLC/IP3/Ca2+ signaling induces contraction. Also activates CCK1R on pancreatic acinar cells (enzyme secretion) and CCK2R on gastric parietal cells (acid secretion at high doses). Diagnostic hepatobiliary scintigraphy: 0.02 mcg/kg IV over 30-60 min during HIDA scan — gallbladder ejection fraction <35% suggests chronic acalculous cholecystitis. Rapid injection (<1 min) can cause cramping and false-positive low ejection fraction. Barium transit: 0.04 mcg/kg IV accelerates small bowel transit. Also used for pancreatic enzyme collection. Half-life ~minutes. Side effects: abdominal cramping, nausea (dose-related CCK effects).
Effects
## Gastrointestinal/Gallbladder System [Tier 1 - FDA-Approved Diagnostic] - Synthetic C-terminal octapeptide of cholecystokinin (CCK-8), the endogenous hormone that triggers gallbladder contraction after fat intake - Stimulates gallbladder contraction (ejection fraction measurement via HIDA scan is the primary diagnostic use) - Stimulates pancreatic enzyme secretion (lipase, amylase, proteases) by acting on CCK-1 receptors on acinar cells - Accelerates small intestinal transit time by stimulating segmental contractions - Relaxes the sphincter of Oddi, facilitating biliary and pancreatic drainage ## Central Nervous System [Tier 1 - Human Data] - CCK is a potent satiety signal — CCK-1 receptor activation on vagal afferents sends satiety signals to the nucleus tractus solitarius - IV sincalide produces rapid and profound satiety/fullness sensation at diagnostic doses - Nausea at higher doses reflects CCK's role in the emetic reflex arc - CCK-2 (gastrin) receptor activation in the brain may modulate anxiety (anxiogenic at high doses in animal models) ## Hepatobiliary System [Tier 1 - Human Data] - Choleretic effect: increases bile flow volume - Clinical utility in biliary dyskinesia diagnosis: gallbladder ejection fraction <35% after sincalide infusion suggests motility disorder - Used pre-operatively to assess gallbladder function before cholecystectomy consideration ## Gastrointestinal/Pancreatic System [Tier 1 - Human Data] - Potent stimulator of pancreatic exocrine secretion - Used in combination with secretin for complete pancreatic function testing - Stimulates intestinal brush border enzyme release and mucosal blood flow
Practitioner Guide
## Clinical Context Sincalide is a diagnostic agent, not a therapeutic peptide used in optimization clinics. It is FDA-approved (Kinevac) for gallbladder function testing and bowel preparation for imaging. ## FDA-Approved Uses - HIDA scan augmentation: 0.02mcg/kg IV over 30-60 minutes to stimulate gallbladder contraction - Barium enema preparation: accelerates colonic evacuation - Duodenal intubation: stimulates bile flow for aspiration studies ## Who Asks About Sincalide - Patients with biliary dyskinesia or gallbladder motility issues - Patients interested in enhancing digestive enzyme secretion naturally - Biohackers interested in CCK pathway modulation for appetite control ## Practical Guidance for Patients - This is not a take-home peptide. It is an IV diagnostic agent administered in radiology departments. - For patients wanting CCK pathway benefits: eating fat and protein triggers endogenous CCK release. A high-protein, moderate-fat meal is the simplest "CCK protocol." - For gallbladder support: consider ox bile supplements, artichoke extract (stimulates bile flow), or phosphatidylcholine - For appetite control via CCK pathways: high-protein meals, fiber intake, and eating slowly all naturally enhance CCK release ## No Peptide Therapy Application - Not available in compounding pharmacies for SC injection - No established off-label protocols - Safer and more practical to optimize endogenous CCK through diet
Research Summary
## Tier 1 — Human Clinical Data - FDA-approved diagnostic agent (Kinevac) with decades of clinical use - Well-characterized pharmacology: dose-dependent gallbladder contraction with ejection fraction as quantifiable endpoint - Safety profile well-established: nausea, abdominal cramping, and urgency are expected effects at diagnostic doses - No serious adverse events at standard diagnostic doses; rare hypersensitivity ## Tier 2 — Human Physiological Data - CCK-8 (sincalide) is the most potent endogenous satiety signal per calorie of food stimulus - IV CCK infusion reduces meal size and duration in human feeding studies - CCK-induced satiety is primarily vagal (CCK-1 receptor on vagal afferents) — this pathway is exploited by CCK-1 receptor agonists in development for obesity ## Tier 3 — Preclinical - CCK-1 receptor knockout mice are hyperphagic and develop obesity - CCK interacts bidirectionally with leptin signaling (CCK potentiates leptin's satiety effects) - CCK-2 receptor (brain-predominant) mediates anxiogenic effects and has been explored as a target for anxiety research ## Evidence Gaps - No therapeutic human trials for obesity or appetite control - Subcutaneous or oral bioavailability not established for therapeutic use - Long-term CCK agonism safety unknown (theoretical gallbladder and pancreatic overactivation concerns) - CCK-1 selective agonists for obesity treatment have been explored but not successfully developed to date