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

Authors Keppel Hesselink JM

Received 27 September 2019

Accepted for publication 24 December 2019

Published 15 January 2020 Volume 2020:13 Pages 123—130

DOI https://doi.org/10.2147/JPR.S232714

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Michael A Überall


Jan M Keppel Hesselink 1, 2

1Faculty of Health, University of Witten/Herdecke, Witten, Germany; 2Department Research and Development, Institute for Neuropathic Pain, Bosch en Duin, The Netherlands

Correspondence: Jan M Keppel Hesselink Tel +31651700527
Email jan@neuropathie.nu

Abstract: Ceruletide (CRL) is a decapeptide, originating from the skin of a tropical frog, and is many times more potent that cholecystokinin (CCK) in a number of assays. The compound was first isolated and characterized around 50 years ago, and its analgesic properties were subsequently identified. Since the 1980s it has been available in the clinic as a parenteral solution and is used as a diagnostic tool to characterize pancreas and gall bladder malfunctions. Its analgesic properties were evaluated in a number of indications: cancer pain, burns, colic pains and migraine. Preclinically, CRL reduces pain in low microgram dose range and promotes clear and long-lasting analgesic activity in nanograms when applied centrally. CCK is amongst the most widely expressed neuropeptides in the brain. CCK-induced analgesic effects in response to persistent and inflammatory pain have recently been associated with CCK2 receptor signaling. CRL, a potent CCK agonist, might be worthwhile to rediscover as a putative analgesic drug and could represent a potential analgesic intrathecal strategy to patients with cancer-related pain.

Keywords: caerulein, neuropeptide, pain, cancer, Kambo

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