Nemifitide

{{Short description|Chemical compound}}

{{Drugbox

| IUPAC_name = (4R)-4-hydroxy-L-prolyl-N5-(diaminomethylidene)-L-ornithylglycyl-N-[(2S)-2-amino-3-(4-fluorophenyl)propanoyl]-L-tryptophanamide

| image = Nemifitide.svg

| width = 300

| tradename =

| pregnancy_category =

| legal_status = Non-regulated

| routes_of_administration = Subcutaneous injection

| bioavailability =

| metabolism =

| elimination_half-life = 15-30 minutes{{cite book | vauthors = Foye WO, Lemke TL, Williams DA | title = Foye's principles of medicinal chemistry | url = https://books.google.com/books?id=R0W1ErpsQpkC&pg=PA596 | access-date = 15 July 2016 | date = 1 September 2007 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-6879-5 | page = 596}}

| excretion =

| CAS_number = 173240-15-8

| ATC_prefix = none

| ATC_suffix =

| PubChem = 177265

| ChemSpiderID = 154356

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = RO19OXA9NG

| C=33 | H=43 | F=1 | N=10 | O=6

| smiles = c1ccc2c(c1)c(c[nH]2)C[C@@H](C(=O)N)NC(=O)CNC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H]3C[C@H](CN3C(=O)[C@H](Cc4ccc(cc4)F)N)O

}}

Nemifitide (INN-00835) is a novel antidepressant drug with a pentapeptide structure similar to that of melanocyte-inhibiting factor (MIF-1) and the amino acid sequence 4-F-Phe-4-OH-Pro-Arg-Gly-Trp-NH2.{{cite journal | vauthors = Holtzheimer PE, Nemeroff CB | title = Novel targets for antidepressant therapies | journal = Current Psychiatry Reports | volume = 10 | issue = 6 | pages = 465–473 | date = December 2008 | pmid = 18980729 | pmc = 4413474 | doi = 10.1007/s11920-008-0075-5 }} It is under development by Tetragenex (previously Innapharma, Inc.) for the treatment of major depressive disorder.{{cite web | url = http://www.tetragenex.com/technology.html | archive-url = https://web.archive.org/web/20120325160140/http://www.tetragenex.com/technology.html | url-status = dead | archive-date = 2012-03-25 | title = Tetragenex Pharmaceuticals Inc. - Product Technology - Nemifitide | access-date = 2011-06-13}} It has been given to over 430 people over the course of 12 clinical trials throughout a little over the past decade and has reached Phase III studies, but has not yet been approved for marketing in any country.

Nemifitide has shown mixed efficacy in alleviating depressive symptoms,{{cite journal | vauthors = Rakofsky JJ, Holtzheimer PE, Nemeroff CB | title = Emerging targets for antidepressant therapies | journal = Current Opinion in Chemical Biology | volume = 13 | issue = 3 | pages = 291–302 | date = June 2009 | pmid = 19501541 | pmc = 4410714 | doi = 10.1016/j.cbpa.2009.04.617 }}{{cite book | author = Renato D. Alarcón | title = Antidepressants: past, present, and future | url = https://books.google.com/books?id=sO_hArhCxwMC&pg=PA575 | year = 2004 | publisher = Springer | isbn = 978-3-540-43054-4 | page = 575}} but in the cases in which it has worked it has proven to have a rapid onset of action (~5–7 days), few to no side effects, and an excellent safety profile. However, it is inactive orally and must be administered via subcutaneous injection. Remarkably, despite having a very short half-life of only 15–30 minutes, in most or all studies assessing its efficacy nemifitide has been administered merely once daily via the subcutaneous route and yet is effective for depression.

The mechanism of action of nemifitide is unclear, but since MIF-1 has been demonstrated to have similar antidepressant effects{{cite journal | vauthors = van der Velde CD | title = Rapid clinical effectiveness of MIF-I in the treatment of major depressive illness | journal = Peptides | volume = 4 | issue = 3 | pages = 297–300 | year = 1983 | pmid = 6138756 | doi = 10.1016/0196-9781(83)90136-5 | s2cid = 54412069 }} it may act in an analogous manner. Possibly of interest however is that nemifitide binds to several receptors including 5-HT2A (where it has been shown to act as an antagonist), NPY1, bombesin, and MC4 and MC5, though at only micromolar concentrations. Whether any of these relatively weak actions are of any clinical significance is unclear.

See also

References

{{Reflist}}

Further reading

  • {{cite journal | vauthors = Dingemanse J | title = Nemifitide. Innapharma | journal = Current Opinion in Investigational Drugs | volume = 4 | issue = 7 | pages = 859–862 | date = July 2003 | pmid = 14619408 }}

{{Antidepressants}}

{{Use dmy dates|date=April 2017}}

Category:Antidepressants

Category:Pentapeptides

Category:Drugs with unknown mechanisms of action