Dirlotapide
{{Short description|Chemical compound}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 443642508
| IUPAC_name = 1-Methyl-N-[(1S)-2-(methyl-(phenylmethyl)amino)-2-oxo-1-phenylethyl]-5-[
| image = Dirlotapide structure.svg
| image2 = Dirlotapide ball-and-stick model.png
| width = 260
| tradename = Slentrol
| Drugs.com = {{drugs.com|international|dirlotapide}}
| pregnancy_AU =
| pregnancy_category =
| routes_of_administration = By mouth
| ATCvet = yes
| ATC_prefix = A08
| ATC_suffix = AB91
| legal_AU =
| legal_CA = Rx-only
| legal_CA_comment =
| legal_UK =
| legal_US = Rx-only
| legal_status =
| bioavailability =
| metabolism = Liver
| elimination_half-life = 5–18 hours (increased with repeated dosing)
| excretion = Feces, urine
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 481658-94-0
| PubChem = 9917862
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank =
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 8093509
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 578H0RMP25
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D03867
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 410414
| C=40 | H=33 | F=3 | N=4 | O=3
| smiles = FC(F)(F)c1ccc(cc1)c2ccccc2C(=O)Nc3cc4c(cc3)n(c(c4)C(=O)N[C@@H](c5ccccc5)C(=O)N(Cc6ccccc6)C)C
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C40H33F3N4O3/c1-46(25-26-11-5-3-6-12-26)39(50)36(28-13-7-4-8-14-28)45-38(49)35-24-29-23-31(21-22-34(29)47(35)2)44-37(48)33-16-10-9-15-32(33)27-17-19-30(20-18-27)40(41,42)43/h3-24,36H,25H2,1-2H3,(H,44,48)(H,45,49)/t36-/m0/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = TUOSYWCFRFNJBS-BHVANESWSA-N
}}
Dirlotapide is a drug used to treat obesity in dogs. It is manufactured by Pfizer and Zoetis and marketed under the brand name Slentrol.{{cn|date=August 2023}}
It works as a gut-selective microsomal triglyceride transfer protein (MTTP or MTP) inhibitor.{{cite patent | country = US | number = 20160002264 | url=http://www.freepatentsonline.com/y2016/0002264.html | title=Carbocyclic- and Heterocyclic-Substituted Hexahydropyrano[3,4-d][1,3]Thiazin-2-Amine Compounds | assign1 = Pfizer, Inc. }} This blocks the assembly and release of lipoproteins into the bloodstream, thereby reducing fat absorption.{{medcn|date=August 2023}} It also elicits a satiety signal from lipid-filled cells lining the intestine.{{medcn|date=August 2023}}
Usage
It is supplied as an oral solution. It is not intended for use in humans, cats, birds, rodents, or other animals.
Dirlotapide is used to manage obesity in dogs and helps by reducing appetite. It is used as part of an overall weight control program that also includes proper diet and exercise, under the supervision of a veterinarian. Side effects may include vomiting, diarrhea, lethargy, drooling, or uncoordination. Allergic reaction to the medication may include, facial swelling, hives, scratching, sudden onset of diarrhea, vomiting, shock, seizures, pale gums, cold limbs, or coma.
Regulation and safety
On January 5, 2007, the U.S. Food and Drug Administration (FDA) approved Slentrol, the first time the FDA has approved a drug for obese dogs.{{cite journal | vauthors = Klonoff DC | title = Dirlotapide, a U.S. Food and Drug Administration-approved first-in-class obesity drug for dogs-will humans be next? | journal = Journal of Diabetes Science and Technology | volume = 1 | issue = 3 | pages = 314–6 | date = May 2007 | pmid = 19885086 | pmc = 2769592 | doi = 10.1177/193229680700100301 }}{{cite news|url=https://news.yahoo.com/s/ap/20070106/ap_on_he_me/doggie_diet_drug |title=FDA approves 1st drug for obese dogs |first=Andrew |last=Bridges | name-list-style = vanc |access-date=January 6, 2007 |agency=Associated Press |via=Yahoo! News |archive-url=https://web.archive.org/web/20070108052816/http://news.yahoo.com/s/ap/20070106/ap_on_he_me/doggie_diet_drug |archive-date=2007-01-08 |url-status=dead }}
However, concerns have since been raised, since 2010, about adverse effects{{cite news |last1=Edwards |first1=Jim | name-list-style = vanc |title=Why Pfizer Doesn't Want the FDA Studying Its Diet Drug for Dogs |url=https://www.cbsnews.com/news/why-pfizer-doesnt-want-the-fda-studying-its-diet-drug-for-dogs/ |access-date=2018-07-05 |work=CBS News |date=15 October 2010 }} that might more strongly affect particular breeds.{{cite news |last1=Hobson |first1=Katherine | name-list-style = vanc |title=FDA Sniffing Around Pfizer's Doggy Weight-Loss Drug Slentrol |url=https://blogs.wsj.com/health/2010/10/14/fda-sniffing-around-pfizers-doggy-weight-loss-drug-slentrol/ |access-date=2018-07-05 |work=WSJ |date=14 October 2010}}
Dirlotapide (under the brand name Slentrol) was authorized for use in the EU by the European Medicines Agency for helping weight loss in dogs, but has since been withdrawn from the market in the EU.{{cite journal | vauthors = German AJ | title = Weight management in obese pets: the tailoring concept and how it can improve results | journal = Acta Veterinaria Scandinavica | volume = 58 | issue = Suppl 1 | pages = 57 | date = October 2016 | pmid = 27766974 | pmc = 5073926 | doi = 10.1186/s13028-016-0238-z | doi-access = free }}
References
{{reflist}}
{{Antiobesity preparations}}
{{Lipid modifying agents}}