Endocannabinoid reuptake inhibitors (eCBRIs), also called cannabinoid reuptake inhibitors (CBRIs), are drugs which limit the reabsorption of endocannabinoid neurotransmitters by the releasing neuron.[1][2]
Pharmacology
Endocannabinoid uptake inhibitors that bind to fatty acid-binding proteins (FABPs) have been described.[1] The inhibition of endocannabinoid reuptake raises the amount of those neurotransmitters available in the synaptic cleft and therefore increases neurotransmission. Following the increase of neurotransmission in the endocannabinoid system is the stimulation of its functions which, in humans, include: suppression of pain perception (analgesia), increased appetite, mood elevation and inhibition of short-term memory.[3][4]
Examples of eCBRIs
- AM404[2] - an active metabolite of Paracetamol.
- AM1172[5]
- LY-2183240[6]
- O-2093
- OMDM-2
- UCM-707
- VDM-11
- Guineensine[7]
- WOBE437 and RX-055[8][9]
See also
- Endocannabinoid enhancer
- Endocannabinoid system
- Reuptake inhibitor
- Cannabinoid receptor antagonist
- Endocannabinoid transporters
- FAAH inhibitor
- MAGL inhibitor
References
- ^ a b Berger WT, Ralph BP, Kaczocha M, Sun J, Balius TE, Rizzo RC, Haj-Dahmane S, Ojima I, Deutsch DG (2012). "Targeting fatty acid binding protein (FABP) anandamide transporters - a novel strategy for development of anti-inflammatory and anti-nociceptive drugs". PLOS ONE. 7 (12): e50968. Bibcode:2012PLoSO...750968B. doi:10.1371/journal.pone.0050968. PMC 3517626. PMID 23236415.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b Costa B, Siniscalco D, Trovato AE, Comelli F, Sotgiu ML, Colleoni M, Maione S, Rossi F, Giagnoni G (2006). "AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain". Br. J. Pharmacol. 148 (7): 1022–32. doi:10.1038/sj.bjp.0706798. PMC 1751928. PMID 16770320.
- ^ "Endocannabinoid System".
- ^ Chicca, Andrea; Nicolussi, Simon; Bartholomäus, Ruben; Blunder, Martina; Aparisi Rey, Alejandro; Petrucci, Vanessa; Reynoso-Moreno, Ines del Carmen; Viveros-Paredes, Juan Manuel; Dalghi Gens, Marianela; Lutz, Beat; Schiöth, Helgi B.; Soeberdt, Michael; Abels, Christoph; Charles, Roch-Philippe; Altmann, Karl-Heinz; Gertsch, Jürg (20 June 2017). "Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake". Proceedings of the National Academy of Sciences of the United States of America. 114 (25): E5006–E5015. doi:10.1073/pnas.1704065114. ISSN 0027-8424. PMC 5488949. PMID 28584105.
- ^ Glaser ST, Kaczocha M, Deutsch DG (Aug 2005). "Anandamide transport: a critical review". Life Sci. 77 (14): 1584–604. doi:10.1016/j.lfs.2005.05.007. PMID 15979096.
- ^ Moore SA, Nomikos GG, Dickason-Chesterfield AK, Schober DA, Schaus JM, Ying BP, Xu YC, Phebus L, Simmons RM, Li D, Iyengar S, Felder CC (2005). "Identification of a high-affinity binding site involved in the transport of endocannabinoids.". Proceedings of the National Academy of Sciences. 102 (49): 17852–7. doi:10.1073/pnas.0507470102. PMC 1295594. PMID 16314570.
- ^ Nicolussi S, Viveros-Paredes JM, Gachet MS, Rau M, Flores-Soto ME, Blunder M, Gertsch J (Feb 2014). "Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice". Pharmacol. Res. 80: 52–65. doi:10.1016/j.phrs.2013.12.010. PMID 24412246.
- ^ Chicca A, Nicolussi S, Bartholomäus R, Blunder M, Aparisi Rey A, Petrucci V, Reynoso-Moreno ID, Viveros-Paredes JM, Dalghi Gens M, Lutz B, Schiöth HB, Soeberdt M, Abels C, Charles RP, Altmann KH, Gertsch J (2017). "Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake". Proc Natl Acad Sci U S A. 55 (25): E5006–E5015. doi:10.1073/pnas.1704065114. PMC 5488949. PMID 28584105.
- ^ Nicolussi S, Chicca A, Soeberdt M, Abels C, Viveros.Paredes JM, Aparisi-Rey A, Lutz B, Gertsch J. WOBE437 - Prototype of a novel class of potent, selective endocannabinoid reuptake inhibitors. BPS 6th Eur Workshop on Cannabinoid Research 2013.