A Placebo-controlled Trial of L-365,260, a CCKB Antagonist, in Panic Disorder
Overview
Authors
Affiliations
The functional role of cholecystokinin in the central nervous system is unknown. The tetra peptide CCK-4 was previously observed to induce panic attacks in a majority of normal volunteers and patients with panic disorder. Furthermore, it had been demonstrated that pretreatment with 10-50 mg of L-365,260, a selective CCKB antagonist, blocked CCK-4 induced panic in patients with panic disorder. Therefore, the present multicenter, placebo-controlled, double-blind trial was designed to investigate the efficacy of L-365,260, a CCKB antagonist, in patients with panic disorder with or without agoraphobia. Following a 1-week, single-blind placebo period, 88 patients were randomized to double-blind treatment in which they received either L-365,260, 30 mg qid, or placebo for 6 weeks. At the dose tested, there were no clinically significant differences between L-365,260 and placebo in global improvement ratings, Hamilton anxiety rating scale scores, panic attack frequency, panic attack intensity, or disability measures. The possible reasons for lack of effect with L-365,260 are discussed.
Kunamneni A, Montera M, Durvasula R, Alles S, Goyal S, Westlund K Int J Mol Sci. 2023; 24(13).
PMID: 37446213 PMC: 10341521. DOI: 10.3390/ijms241311035.
Structural insights into human brain-gut peptide cholecystokinin receptors.
Ding Y, Zhang H, Liao Y, Chen L, Ji S, Qin J Cell Discov. 2022; 8(1):55.
PMID: 35672283 PMC: 9174195. DOI: 10.1038/s41421-022-00420-3.
Cholecystokinin and Panic Disorder: Reflections on the History and Some Unsolved Questions.
Rehfeld J Molecules. 2021; 26(18).
PMID: 34577128 PMC: 8469898. DOI: 10.3390/molecules26185657.
Single-chain Fragment variable antibody targeting cholecystokinin-B receptor for pain reduction.
Westlund K, Montera M, Goins A, Alles S, Afaghpour-Becklund M, Bartel R Neurobiol Pain. 2021; 10:100067.
PMID: 34458647 PMC: 8378781. DOI: 10.1016/j.ynpai.2021.100067.
Potential gut-brain mechanisms behind adverse mental health outcomes of bariatric surgery.
Brown R, Guerrero-Hreins E, Brown W, le Roux C, Sumithran P Nat Rev Endocrinol. 2021; 17(9):549-559.
PMID: 34262156 DOI: 10.1038/s41574-021-00520-2.