Inhibition of P‐glycoprotein by psychotherapeutic drugs in a canine cell model

• Published in: Journal of veterinary pharmacology and therapeutics Vol. 37; no. 5; pp. 515 - 517
• Main Authors: Schrickx, J. A, Fink‐Gremmels, J
• Format: Journal Article
• Language: English
• Published: England Blackwell Scientific Publications 01.10.2014; Blackwell Publishing Ltd
• Subjects: Animals; antidepressants; anxiety; ATP-Binding Cassette, Sub-Family B, Member 1 - genetics; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; behavior disorders; Cell Line; Clomipramine - pharmacology; Dogs; Fluoxetine - pharmacology; Gene Expression Regulation - drug effects; mechanism of action; Monoamine Oxidase Inhibitors - pharmacology; Selegiline - pharmacology; serotonin; Serotonin Uptake Inhibitors - pharmacology
• ISSN: 0140-7783; 1365-2885
• DOI: 10.1111/jvp.12111

Drug–drug interactions related to long‐term therapies are of increasing concern. Psychotherapeutic drugs, licensed for the use in dogs for the management of separation anxiety and other behavioural disorders, are examples of drugs used in long‐term therapies. In an in vitro system with canine P‐glycoprotein (P‐gp) expressing cell lines, three psychotherapeutic drugs with a different mode of action were tested for their ability to inhibit the canine multidrug transporter P‐gp. At 10 μm, the selective serotonin reuptake inhibitor fluoxetine and the tricyclic antidepressant clomipramine inhibited P‐gp for 41% and 59%, respectively. In contrast, selegeline did not inhibit the function of the canine P‐gp.