Rediscovery of Ceruletide, a CCK Agonist, as an Analgesic Drug

Figures & data

Figure 1 PubMed indexed papers on CRL – search results 12-12-2018.

Figure 2 Structure of the decapeptide CRL diethylamine (PubChem, open chemistry database).

Table 1 Summarized Details of All Studies Reviewed

Study	Indication	Method and # Patients	Dose and Administration	Total Dose/Adult 70 kg	Result
Erspamer (1967)^Citation13	Healthy volunteers	Open; not specified	IV bolus 1–2 ng/kg BW	70–140 ng	Contraction gall bladder
Stacher (1982)^Citation22	Healthy volunteers	DB Placebo RCT N=24	IV infusions of 6, 60 and 120 ng/kg BW/hour	420–4200-8400 ng	60 and 120 ng/kg BW/hour significant pain reduction
Basso (1982)^Citation23	Claudication and rest pain	DB Placebo RCT N=8	IV infusion of one minute of 1, 2 or 4 ng/kg BW	70-140-280 ng	Rest pain significantly abolished
Dolecek et al (1983)^Citation24	Mixed pain states (cancer, myocardial infarction, burns)	Open case collection N=45	IV infusion of 5 mcg (5000 ng) in 30 mins, twice daily	5000 ng	Complete disappearance of pain was reported in 24 patients
Malfertheiner (1983)^Citation29	Migraine	Open N=3	IV infusion of CRL 2 ng/kg BW/min	140 ng	Substantial pain decline
Pardo (1984)^Citation30	Biliary colic pains	DB Placebo RCT N=60	IV infusion of 1 ng/kg IV in 1 min	70 ng	Significant pain reduction
Stacher (1984)^Citation31	Healthy volunteers	Placebo RCT N=16	IM injection 5, 10, or 20 mcg (5000–10.000 and 20.000 ng)	5000–10.000 and 20.000 ng	Significant pain reduction in challenge paradigm
Basso (1985)^Citation32	Biliary colic pain	DB Placebo RCT N=24	IV infusion of 1 ng/kg BW in 90 seconds	70 ng	Significant pain reduction
Meyer-Lindau (1988)^Citation33	Cancer patients	DB RCT N=36	IM injection 5 mcg (5000 ng) versus morphine	5000 ng	Comparable effect
Gullo (1988)^Citation35	Pancreas patients	Open, N=6	50 and 100 ng/kg BW/hour	3500 ng 7000 ng	High dose gave more pancreatic stimulation
Pause (1996)^Citation34	Healthy men	Placebo controlled DB RCT N=25	IV 0.5 and 5 mcg in 30 mins	500 and 5000 ng	Significant reduction heat pain, enhanced sensitivity to mechanically induced pain

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Pardo A, Celotti F, De Paolis C. Ceruletide analgesia in biliary colic. Clin Pharmacol Ther. 1984;36:510–514. doi:10.1038/clpt.1984.211

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Stacher G, Steinringer H, Schmierer G, et al. Ceruletide increases dose dependently both jejunal motor activity and threshold and tolerance to experimentally induced pain in healthy man. Gut. 1984;25:513–519. doi:10.1136/gut.25.5.513

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Basso N, Bagarani M, Materia A, et al. Effect of caerulein in patients with biliary colic pain. Gastroenterology. 1985;89:605–609. doi:10.1016/0016-5085(85)90457-3

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Meyer-Lindau F, Pfister E, Gyr N, et al. Randomized double-blind study of the analgesic effect of caerulein and morphine in chronic tumor pain. Onkologie. 1988;11:77–80. doi:10.1159/000216492

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Gullo L. Maximal effective dose of cerulein in the secretin-cerulein test. Digestion. 1988;39:225–229. doi:10.1159/000199630

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Pause BM, Drews C, Scherhag C, et al. Analgesic effect of ceruletide in men is limited to specific pain qualities. Physiol Behav. 1996;59:1025–1031. doi:10.1016/0031-9384(95)02230-9

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