Abstract
The endocannabinoid system (ECS) plays a crucial role in numerous physiological processes in the central and peripheral nervous systems. In the gastrointestinal (GI) tract, selective cannabinoid (CB) receptor agonists exert potent inhibitory actions on motility and pain signalling. In the present study, we used mouse models of diarrhea, hypermotility, and abdominal pain to examine whether a novel synthetic CB1 receptor agonist AM9405 [(2-(2,6-dihydroxy 4 (2-methyloctan-2-yl) phenyl) - 1,3-dimethy1-1H-benzo [d]imidazol-3-ium bromide);also known as GAT379] exhibits effects of potential therapeutic relevance. AM9405 significantly slowed mouse intestinal motility in physiological conditions. Moreover, AM9405 reversed hypermotility and reduced pain in mouse models mimicking symptoms of functional GI disorders, such as stress-induced diarrhea and writhing test. Interestingly, some of the effects of AM9405 were blocked by a 5-HT3 antagonist suggesting interaction with 5-HT3 receptors. In our study we show that combining Ca-1 agonism with 5-HT3 agonism may alter physiological functions and experimental pathophysiologies in a manner that make such compounds promising drugs for the future treatment of functional GI disorders.
Item Type: | Journal article |
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Faculties: | Medicine |
Subjects: | 600 Technology > 610 Medicine and health |
ISSN: | 0014-2999 |
Language: | English |
Item ID: | 63454 |
Date Deposited: | 19. Jul 2019, 12:13 |
Last Modified: | 04. Nov 2020, 13:41 |