Delavirdine (DLV) (brand name Rescriptor) is a non-nucleoside

reverse transcriptase inhibitor Reverse-transcriptase inhibitors (RTIs) are a class of antiretroviral drugs used to treat HIV infection or AIDS, and in some cases hepatitis B. RTIs inhibit activity of reverse transcriptase, a viral DNA polymerase that is required for replicati ...

(NNRTI) marketed by

ViiV Healthcare ViiV Healthcare ( ) is a pharmaceutical company specializing in the development of therapies for HIV infection that was created as a joint venture by Pfizer and GlaxoSmithKline in November 2009 with both companies transferring their HIV assets ...

. It is used as part of highly active antiretroviral therapy (HAART) for the treatment of

human immunodeficiency virus The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...

(HIV) type 1. It is presented as the

mesylate In organosulfur chemistry, a mesylate is any salt or ester of methanesulfonic acid (). In salts, the mesylate is present as the anion. When modifying the international nonproprietary name of a pharmaceutical substance containing the group ...

. The recommended dosage is 400 mg, three times a day. Although delavirdine was approved by the U.S.

Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...

in 1997, its efficacy is lower than other NNRTIs, especially

efavirenz Efavirenz (EFV), sold under the brand names Sustiva among others, is an antiretroviral medication used to treat and prevent HIV/AIDS. It is generally recommended for use with other antiretrovirals. It may be used for prevention after a needlest ...

, and it also has an inconvenient schedule. These factors have led the U.S. DHHS not to recommend its use as part of initial therapy.DHHS panel. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents (May 4, 2006). (Available for download fro
AIDSInfo
) The risk of cross-resistance across the NNRTI class, as well as its complex set of drug interactions, make the place of delavirdine in second-line and

salvage therapy Salvage therapy, also known as rescue therapy, is a form of therapy given after an ailment does not respond to standard therapy. The most common diseases that require salvage therapy are HIV and various cancers. The term is not clearly defined; it ...

unclear, and it is currently rarely used. Its manufacturing and distribution was discontinued in the United States and Canada.

Interactions

ritonavir Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor a ...

, delavirdine is an inhibitor of

cytochrome P450 Cytochromes P450 (CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that functions as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are ...

isozyme

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from t ...

, and interacts with many medications. It should not be administered with a wide range of drugs, including

amprenavir Amprenavir (original brand name Agenerase, GlaxoSmithKline) is a protease inhibitor (pharmacology), protease inhibitor used to treat HIV infection. It was approved by the Food and Drug Administration on April 15, 1999, for twice-a-day dosing in ...

fosamprenavir Fosamprenavir, sold under the brand names Lexiva and Telzir, is a medication used to treat HIV/AIDS. It is a prodrug of the protease inhibitor (pharmacology), protease inhibitor and antiretroviral drug amprenavir. It is marketed by ViiV Healthcare ...

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease elevated lipid levels. It is also used to decrease the risk of heart ...

lovastatin Lovastatin, sold under the brand name Mevacor among others, is a statin medication, to treat hypercholesterolemia, high blood cholesterol and reduce the risk of cardiovascular disease. Its use is recommended together with lifestyle changes. It ...

rifampin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. It is almost always used tog ...

rifabutin Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat ''Mycobacterium avium'' complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals. For active tuber ...

rifapentine Rifapentine, sold under the brand name Priftin, is an antibiotic used in the treatment of tuberculosis. In active tuberculosis it is used together with other antituberculosis medications. In latent tuberculosis it is typically used with isoniaz ...

St John's wort ''Hypericum perforatum'', known as St. John's wort, is a flowering plant in the family Hypericaceae and the type species of the genus ''Hypericum''. Possibly a hybrid between '' H. maculatum'' and '' H. attenuatum'', the species can be found a ...

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia and procedural sedation, and to treat severe agitation. It works by inducing sleepiness, decreasing anxiety, and causing a loss of a ...

triazolam Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties ...

ergot Ergot ( ) or ergot fungi refers to a group of fungi of the genus ''Claviceps''. The most prominent member of this group is ''Claviceps purpurea'' ("rye ergot fungus"). This fungus grows on rye and related plants, and produces alkaloids that ca ...

medications, and several medications for

acid reflux Gastroesophageal reflux disease (GERD) or gastro-oesophageal reflux disease (GORD) is one of the upper gastrointestinal chronic diseases where stomach content persistently and regularly flows up into the esophagus, resulting in symptoms and/ ...

Adverse effects

The most common adverse event is moderate to severe

rash A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

, which occurs in up to 20% of patients. Other common adverse events include

fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...

headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...

and

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

. Liver toxicity has also been reported.

Synthesis

Modification of the scheme that was done for

ateviridine Ateviridine is a non-nucleoside reverse transcriptase inhibitor that has been studied for the treatment of HIV. Synthesis Preparation of the pyridylpiperazine moiety starts by aromatic displacement of chlorine from 2-chloro-3-nitropyridine by p ...

q.v. } (right to left). , - , ''quo errat demonstrator'', , where the prover errs, , A pun on "quod erat demonstrandum" , - , ''quo fata ferunt'', , where the fates bear us to, , motto of Bermuda , - , ''quo non ascendam'' , , to what heights can I ...

by performing the reductive alkylation with acetone gives 2 after removal of the protecting group. Acylation of this amine with the imidazolide from 5-Methylsulfonaminoindole-2-carboxylic acid (1) affords the amide,

, atevirdine.

References

External links

* {{Portal bar , Medicine , Viruses CYP2D6 inhibitors CYP3A4 inhibitors Hepatotoxins Non-nucleoside reverse transcriptase inhibitors Pfizer brands Aminopyridines Piperazines Carboxamides Indoles Sulfonamides