Trends in Pharmacological Sciences
Research FocusPossible involvement of the endocannabinoid system in the actions of three clinically used drugs
Section snippets
Modulation of endocannabinoid function in experimental animals in vivo by propofol, indomethacin and flurbiprofen
Recent reports have suggested that CB1 receptor activation might be involved in the actions of three drugs used clinically. Patel et al. [5] investigated the pharmacology of the anaesthetic agent propofol in the mouse. They found that treatment with the CB1 receptor antagonist rimonabant [SR141716A (see Chemical names)] reduced (but did not remove) the incidence of the loss of the righting reflex induced by a sedative dose of propofol [100 mg kg−1 by intraperitoneal injection (i.p.)], whereas
Involvement of fatty acid amide hydrolase (FAAH)
Elucidation of the mechanism of these endocannabinoid effects is of considerable importance because it could suggest a therapeutically viable target. One obvious such target would be fatty acid amide hydrolase (FAAH), the enzyme responsible for the metabolism of anandamide, given that mice lacking this enzyme show a reduced pain sensitivity in both thermal and inflammatory models of pain [10]. Propofol was shown to inhibit FAAH in vitro with an IC50 value of 52 μM, and increase the brain
Conclusions and future perspectives
Recent studies provide evidence that three drugs, propofol, indomethacin and flurbiprofen, affect endocannabinoid function in vivo, and that this modulation can contribute to their pharmacological effects. The key word here is ‘contribute’; it would be too simplistic to attribute their pharmacological actions solely to effects on endocannabinoid function. Furthermore, it is a large step to take to extrapolate data in experimental animals to the situation in humans. Nevertheless, the data do
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Cited by (53)
Propofol reduces microglia activation and neurotoxicity through inhibition of extracellular vesicle release
2019, Journal of NeuroimmunologyNeuropharmacology
2017, Essentials of NeuroanesthesiaGABA(A) receptor Pi (GABRP) stimulates basal-like breast cancer cell migration through activation of extracellular-regulated kinase 1/2 (ERK1/2)
2014, Journal of Biological ChemistryCitation Excerpt :While it is possible that this cell line expresses GABRP protein in the absence of high levels of mRNA, it is more likely that propofol induces migration of these cells through GABA(A) receptors lacking the pi subunit. Alternatively, propofol has been reported to inhibit sodium channels as well as impact endocannabinoid metabolism, and these pathways may also contribute to its effects on MDA-MB-468 cells (44, 45). Our studies reveal that HCC1187 cells do not mobilize calcium in response to GABA stimulation suggesting that GABRP may act in a ligand-independent manner, or that these cells intrinsically produce high quantities of GABA.
Synergistic activation of lipopolysaccharide-stimulated glial cells by propofol
2013, Biochemical and Biophysical Research CommunicationsCitation Excerpt :The classical mechanism of propofol action includes the potentiation of GABAA receptor activity and blockade of sodium channel, none of which is directly involved in the activation of MAPK pathways or inflammatory stimulation in astrocytes. Recently, it has been suggested that endocannabinoid system is involved in the anesthetic and other unique features of propofol [23]. It has been suggested that propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase [24–26], which might be associated with the propofol’s effects on memory formation and anti-nociceptive effects.