Endocannabinoid reuptake inhibitor

Short description: Class of drugs

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]

## Contents

* 1 Pharmacology
* 2 Examples of eCBRIs
* 3 See also
* 4 References

## Pharmacology

The method of transport of endocannabinoids through the cell membrane and cytoplasm to their respective degradation enzymes has been rigorously debated for nearly two decades, and a putative endocannabinoid membrane transporter was proposed.[3] However, as lipophilic molecules endocannabinoids readily pass through the cell lipid bilayer without assistance and would more likely need a chaperone through the cytoplasm to the endoplasmic reticulum where the enzyme FAAH is located. More recently fatty acid-binding proteins (FABPs) and heat shock proteins (Hsp70s) have been described and verified as such chaperones, and their inhibitors have been synthesized.[1][4] 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.[5][6]

## Examples of eCBRIs

* AM404[2] – active metabolite of paracetamol (acetaminophen)
* AM1172[7]
* Guineensine[8]
* LY-2183240[9]
* O-2093
* OMDM-2
* RX-055[10]
* SYT-510[11]
* UCM-707
* VDM-11
* WOBE437[10][12]

## See also

* Endocannabinoid enhancer
* Endocannabinoid system
* Reuptake inhibitor
* Cannabinoid receptor antagonist
* Endocannabinoid transporters
* FAAH inhibitor
* MAGL inhibitor

## References

1. ↑ 1.0 1.1 "Targeting fatty acid binding protein (FABP) anandamide transporters - a novel strategy for development of anti-inflammatory and anti-nociceptive drugs". PLOS ONE 7 (12). 2012. doi:10.1371/journal.pone.0050968. PMID 23236415. Bibcode: 2012PLoSO...750968B.
2. ↑ 2.0 2.1 "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. 2006. doi:10.1038/sj.bjp.0706798. PMID 16770320.
3. ↑ Nicolussi, Simon; Gertsch, Jürg (2015). "Endocannabinoid Transport Revisited". Vitamins & Hormones 98 (14): 441–485. doi:10.1016/bs.vh.2014.12.011. PMID 25817877. https://www.sciencedirect.com/science/article/pii/S0083672914000247. Retrieved 2021-01-17.
4. ↑ Oddi, S.; Fezza, F.; Pasquariello, N.; D'Agostino, A.; Catanzaro, G.; De Simone, C.; Rapino, C.; Finazzi-Agro, A. et al. (2009). "Molecular identification of albumin and Hsp70 as cytosolic anandamide-binding proteins". Chemistry & Biology 16 (6): 624–632. doi:10.1016/j.chembiol.2009.05.004. PMID 19481477.
5. ↑ "Endocannabinoid System". https://terpenoids.net/endocannabinoid-system/.
6. ↑ Chicca, Andrea; Nicolussi, Simon; Bartholomäus, Ruben; Blunder, Martina; Aparisi Rey, Alejandro; Petrucci, Vanessa; Reynoso-Moreno, Ines del Carmen; Viveros-Paredes, Juan Manuel et al. (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. PMID 28584105. Bibcode: 2017PNAS..114E5006C.
7. ↑ "Anandamide transport: a critical review". Life Sci 77 (14): 1584–604. Aug 2005. doi:10.1016/j.lfs.2005.05.007. PMID 15979096.
8. ↑ "Guineensine is a novel inhibitor of endocannabinoid uptake showing cannabimimetic behavioral effects in BALB/c mice". Pharmacol. Res. 80: 52–65. Feb 2014. doi:10.1016/j.phrs.2013.12.010. PMID 24412246.
9. ↑ "Identification of a high-affinity binding site involved in the transport of endocannabinoids.". Proceedings of the National Academy of Sciences 102 (49): 17852–7. 2005. doi:10.1073/pnas.0507470102. PMID 16314570.
10. ↑ 10.0 10.1 "Chemical probes to potently and selectively inhibit endocannabinoid cellular reuptake". Proc Natl Acad Sci U S A 55 (25): E5006–E5015. 2017. doi:10.1073/pnas.1704065114. PMID 28584105. Bibcode: 2017PNAS..114E5006C.
11. ↑ "SYT 510". 22 January 2024. https://adisinsight.springer.com/drugs/800061198.
12. ↑ 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.

* v
* t
* e

Cannabinoid receptor modulators

Receptor
(ligands)</small>|

| CB1|

* Agonists (abridged; see here for more): 2-AG
* 2-AGE (noladin ether)
* 11-Hydroxy-THC
* α-Amyrin · β-Amyrin
* AB-CHMINACA
* AM-1172
* AM-1220
* AM-1221
* AM-1235
* AM-2201
* AM-2232
* Anandamide
* Arvanil
* AZ-11713908
* Cannabinol
* CB-13
* CP 47,497
* CP 55,940
* Dimethylheptylpyran
* DEA
* ECG
* EGCG
* Epicatechin
* Gallocatechol (gallocatechin)
* Honokiol
* HU-210
* JWH-007
* JWH-015
* JWH-018
* JWH-073
* Kavain
* L-759,633
* Levonantradol
* Menabitan
* Nabilone
* Nabitan
* NADA
* O-1812
* Oleamide
* Pravadoline
* Serinolamide A
* THC (dronabinol)
* UR-144
* WIN 55,212-2
* Yangonin

* Antagonists: AM-251
* AM-6545
* Cannabidiol
* Cannabigerol
* Drinabant
* Falcarinol (carotatoxin)
* Hemopressin
* Ibipinabant
* LY-320,135
* MK-9470
* NESS-0327
* O-2050
* Otenabant
* PF-514273
* PipISB
* Rimonabant
* Rosonabant
* Surinabant
* Taranabant
* THCV
* TM-38837
* VCHSR
* Virodhamine

* Antibodies: Brizantin (Бризантин)
* Dietressa (Диетресса)

* Unknown/unsorted: MAFP

|

CB2|

* Agonists: 2-AG
* 2-AGE (noladin ether)
* 3,3'-Diindolylmethane
* 4-O-Methylhonokiol
* α-Amyrin · β-Amyrin
* A-796,260
* A-834,735
* A-836,339
* AM-1172
* AM-1221
* AM-1235
* AM-1241
* AM-2232
* Anandamide
* AZ-11713908
* Cannabinol
* Caryophyllene
* CB-13
* CBS-0550
* CP 55,940
* GW-405,833 (L-768,242)
* GW-842,166X
* HU-308
* JTE 7-31
* JWH-007
* JWH-015
* JWH-018
* JWH-73
* JWH-133
* L-759,633
* L-759,656
* Lenabasum (anabasum)
* Magnolol
* MDA-19
* Nabitan
* NADA
* Olorinab (APD-371)
* PF-03550096
* S-444,823
* SER-601
* Serinolamide A
* UR-144
* Tedalinab
* THC (dronabinol)
* THCV
* Tetrahydromagnolol
* Virodhamine

* Antagonists: 4-O-Methylhonokiol
* AM-630
* BML-190
* Cannabidiol
* Honokiol
* JTE-907
* SR-144,528
* WIN 54,461
* WIN 56,098

NAGly
(GPR18)|

* Agonists: Abnormal cannabidiol
* ACPA
* AM251
* Anandamide
* Cannabidiol
* NADGly
* THC (dronabinol)
* O-1602

* Antagonists: CID-85469571
* O-1918

GPR55|

* Agonists: 2-AGE (noladin ether)
* 2-ALPI
* Abnormal cannabidiol
* AM-251
* CID1011163
* CID1252842
* CID1792579
* CP 55,940
* GSK-494581A
* Lysophosphatidylinositol
* ML-184
* ML-185
* ML-186
* O-1602
* Oleoylethanolamide
* Palmitoylethanolamide
* THC (dronabinol)

* Antagonists: Cannabidiol
* CID-16020046
* ML-191
* ML-192
* ML-193
* O-1918
* PSB-SB-487
* PSB-SB-1202
* PSB-SB-1203
* Tetrahydromagnolol

GPR119|

* Agonists: 2-Oleoylglycerol
* Anandamide
* APD668
* AR-231,453
* AS-1269574
* MBX-2982
* N-Oleoyldopamine
* Oleoylethanolamide
* Olvanil
* PSN-375,963
* PSN-632,408

Unsorted|

* Agonists: Revosimeline

Transporter
(modulators)|

| eCBTs|

* Inhibitors: 5'-DMH-CBD
* AM-404
* AM-1172
* Arachidonoyl serotonin
* Arvanil
* Cannabidiol
* Guineensine
* LY-2183240
* O-2093
* OMDM-2
* Paracetamol (acetaminophen)
* SB-FI-26
* UCM-707
* URB-597
* VDM-11
* WOBE490
* WOBE491
* WOBE492

|

Enzyme
(modulators)|

| FAAH|

* Inhibitors: 4-Nonylphenylboronic acid
* AACOCF3
* AM-404
* Arachidonoyl serotonin
* BIA 10-2474
* Biochanin A
* Genistein
* IDFP
* JNJ-1661010
* JNJ-42165279
* JZL-195
* Kaempferol
* LY-2183240
* MAFP
* Palmitoylisopropylamide
* Paracetamol (acetaminophen)
* PF-3845
* PF-04457845
* PF-750
* SA-47
* SA-57
* TAK 21d
* TC-F 2
* UCM710
* URB-597

* Activators: PDP-EA

|

MAGL|

* Inhibitors: ABX-1431
* IDFP
* JJKK 048
* JW 642
* JZL-184
* JZL-195
* JZP-361
* KML 29
* MAFP
* MJN110
* NAM
* Pristimerin
* URB-602

ABHD6|

* Inhibitors: JZP-169
* JZP-430
* KT182
* KT185
* KT195
* KT203
* LEI-106
* ML294
* ML295
* ML296
* UCM710
* WWL-70

ABHD12|

* Inhibitors: Betulinic acid
* Maslinic acid
* MAFP
* Oleanolic acid
* Orlistat (tetrahydrolipstatin)
* Ursolic acid

Others|

* Precursors: Phosphatidylethanolamine
* NAPE
* Diacylglycerol

* Others: 2-PG (directly potentiates activity of 2-AG at CB1 receptor)
* ARN-272 (FAAH-like anandamide transporter inhibitor)

See also
Receptor/signaling modulators
Cannabinoids (cannabinoids by structure)

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Original source: https://en.wikipedia.org/wiki/Endocannabinoid reuptake inhibitor. Read more

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Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:Endocannabinoid_reuptake_inhibitor&oldid=4038388"
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[CB1]: Cannabinoid receptor type 1
*[CB2]: Cannabinoid receptor type 2
*[NAGly]: N-Arachidonyl glycine receptor
*[GPR18]: G protein-coupled receptor 18
*[GPR55]: G protein-coupled receptor 55
*[GPR119]: G protein-coupled receptor 119
*[eCBTs]: Endocannabinoid transporter
*[FAAH]: Fatty acid amide hydrolase
*[ABHD6]: alpha/beta-Hydrolase domain containing 6
*[ABHD12]: alpha/beta-Hydrolase domain containing 12