Amtolmetin guacil

Amtolmetin guacil
Clinical data
Other names	ST-679
ATC code	none;
Identifiers
	IUPAC name (2-methoxyphenyl) 2-[ [2-[1-methyl-5-(4-methylbenzoyl)pyrrol-2-yl]acetyl]ami;
CAS Number	87344-06-7 ;
PubChem CID	65655;
ChemSpider	59091 ;
UNII	323A00CRO9;
KEGG	D07453 ;
ChEMBL	ChEMBL1766570 ;
CompTox Dashboard (EPA)	DTXSID50236291 ;
ECHA InfoCard	100.207.038
Chemical and physical data
Formula	C24H24N2O5
Molar mass	420.465 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES O=C(c1ccc(n1C)CC(=O)NCC(=O)Oc2ccccc2OC)c3ccc(cc3)C;
	InChI InChI=1S/C24H24N2O5/c1-16-8-10-17(11-9-16)24(29)19-13-12-18(26(19)2)14-22(27)25-15-23(28)31-21-7-5-4-6-20(21)30-3/h4-13H,14-15H2,1-3H3,(H,25,27) ; Key:CWJNMKKMGIAGDK-UHFFFAOYSA-N ;
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Amtolmetin guacil is a non-steroidal anti-inflammatory drug (NSAID). It is a prodrug of tolmetin sodium.^[1]

Background

Tolmetin sodium is an approved NSAID, marketed for the treatment of rheumatoid arthritis, osteoarthritis and juvenile rheumatoid arthritis.^[2] In humans, tolmetin sodium is absorbed rapidly with peak plasma levels observed 30 minutes after administration. It is eliminated rapidly with a mean plasma elimination t_½ of approximately 1 hour. The preparation of slow release formulations or chemical modification of NSAIDs to form prodrugs has been suggested as a method to reduce the gastrotoxicity of these agents.

Amtolmetin guacil is a non-acidic prodrug of tolmetin, having NSAID properties similar to tolmetin with additional analgesic, antipyretic, and gastro protective properties. Amtolmetin is formed by amidation of tolmetin by glycine.

Pharmacology

Most is absorbed on oral administration. It is concentrated in the gastric wall. Highest concentration is reached 2 hours after administration.
Amtolmetin guacil can be hydrolysed to produce the metabolites Tolmetin, MED5 and Guiacol.
Elimination completes in 24 hours. This happens mostly with urine in shape of gluconides products (77%), faecal (7.5%).
It is advised to take the drug on empty stomach.
Permanent anti-inflammatory action continues up to 72 hours, with single administration.

Mechanism of action

Amtolmetin guacil stimulates capsaicin receptors present on gastrointestinal walls, because of presence of vanillic moiety and also releases NO which is gastro protective. It also inhibits prostaglandin synthesis and cyclooxygenase (COX).

References

^ Tsvetkova E, Denisov L, Nasonov E (2017). "AB0798 Amtolmetin guacil-effective and good safe nonsteroidal anti-inflammatory drug in knee osteoarthritis patients with dyspepsia". Annals of the Rheumatic Diseases. 76 (Suppl 2): 1337.2–1337. doi:10.1136/annrheumdis-2017-eular.5253.
^ Garg A, Shoeb A, Moodahadu LS, Sharma A, Gandhi A, Akku S (2016). "Amtolmetin: A Reappraisal of NSAID with Gastroprotection". Arthritis. 2016: 7103705. doi:10.1155/2016/7103705. PMC 4820613. PMID 27092274.

[1] Tsvetkova E, Denisov L, Nasonov E (2017). "AB0798 Amtolmetin guacil-effective and good safe nonsteroidal anti-inflammatory drug in knee osteoarthritis patients with dyspepsia". Annals of the Rheumatic Diseases. 76 (Suppl 2): 1337.2–1337. doi:10.1136/annrheumdis-2017-eular.5253.

[2] Garg A, Shoeb A, Moodahadu LS, Sharma A, Gandhi A, Akku S (2016). "Amtolmetin: A Reappraisal of NSAID with Gastroprotection". Arthritis. 2016: 7103705. doi:10.1155/2016/7103705. PMC 4820613. PMID 27092274.

[1]

[2]

v t e Non-steroidal anti-inflammatory drugs (NSAIDs) (primarily M01A and M02A, also N02BA)
pyrazolones / pyrazolidines	Aminophenazone Ampyrone Azapropazone Clofezone Difenamizole Famprofazone Feprazone Kebuzone Metamizole Mofebutazone Morazone Nifenazone Oxyphenbutazone Phenazone Phenylbutazone Propyphenazone Sulfinpyrazone Suxibuzone^‡
salicylates	Aspirin (acetylsalicylic acid)^# Aloxiprin Benorylate Carbasalate calcium Diflunisal Dipyrocetyl Ethenzamide Guacetisal Magnesium salicylate Methyl salicylate Salsalate Salicin Salicylamide Salicylic acid (salicylate) Sodium salicylate
acetic acid derivatives and related substances	Aceclofenac Acemetacin Alclofenac Amfenac Bendazac Bromfenac Bufexamac Bumadizone Diclofenac Difenpiramide Etodolac Felbinac Fenclozic acid Fentiazac Indometacin Indometacin farnesil Isoxepac Ketorolac Lonazolac Mofezolac Oxametacin Prodolic acid Proglumetacin Sulindac Tiopinac Tolmetin Zomepirac^†
oxicams	Ampiroxicam Droxicam Isoxicam Lornoxicam Meloxicam Piroxicam Pivoxicam Tenoxicam
propionic acid derivatives (profens)	Alminoprofen Benoxaprofen^† Carprofen^‡ Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuprofen^# Ibuproxam Indoprofen^† Ketoprofen Loxoprofen Miroprofen Naproxen Oxaprozin Pelubiprofen Piketoprofen Pirprofen Suprofen Tarenflurbil Tepoxalin^‡ Tiaprofenic acid Vedaprofen^‡ Zaltoprofen COX-inhibiting nitric oxide donator: Naproxcinod
n-arylanthranilic acids (fenamates)	Azapropazone Clonixin Etofenamate Floctafenine Flufenamic acid Flunixin Flutiazin Glafenine^† Meclofenamic acid Mefenamic acid Morniflumate Niflumic acid Tolfenamic acid
COX-2 inhibitors (coxibs)	Apricoxib Celecoxib (+tramadol) Cimicoxib^‡ Deracoxib^‡ Etoricoxib Firocoxib^‡ Lumiracoxib^† Mavacoxib^‡ Parecoxib Robenacoxib^‡ Rofecoxib^† Valdecoxib^†
other	Aminopropionitrile Benzydamine Chondroitin sulfate Diacerein Fluproquazone Glucosamine Glycosaminoglycan Hyperforin Nabumetone Nimesulide Oxaceprol Proquazone Superoxide dismutase / orgotein Tenidap
NSAID combinations	Ibuprofen/famotidine Ibuprofen/hydrocodone Ibuprofen/oxycodone Ibuprofen/paracetamol Meloxicam/bupivacaine Naproxen/diphenhydramine Naproxen/esomeprazole
Key: underline indicates initially developed first-in-class compound of specific group; ^#WHO-Essential Medicines; ^†withdrawn drugs; ^‡veterinary use.
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