Cytochrome P450 2D6 a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotic

Xenobiotic

A xenobiotic is a chemical which is found in an organism but which is not normally produced or expected to be present in it. It can also cover substances which are present in much higher concentrations than are usual...

s in the body. Also, many substances are bioactivated by CYP2D6 to form their active compounds. While CYP2D6 is involved in the oxidation of a wide range of substrates of all the CYPs, there is considerable variability in its expression in the liver. The gene is located near two cytochrome P450 pseudogene

Pseudogene

Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...

s on chromosome 22q13.1. Alternatively spliced

Alternative splicing

Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...

 transcript variants encoding different isoforms have been found for this gene.

Genotype/phenotype variability

CYP2D6 shows the largest phenotypical

Phenotype

A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

 variability among the CYPs, largely due to genetic

Genetics

Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....

 polymorphism

Polymorphism (biology)

Polymorphism in biology occurs when two or more clearly different phenotypes exist in the same population of a species — in other words, the occurrence of more than one form or morph...

. The genotype

Genotype

The genotype is the genetic makeup of a cell, an organism, or an individual usually with reference to a specific character under consideration...

 accounts for normal, reduced, and non-existent CYP2D6 function in subjects.

The CYP2D6 function in any particular subject may be described as one of the following:

• poor metaboliser–these subjects have little or no CYP2D6 function
• intermediate metabolizers–these subjects metabolize drugs at a rate somewhere between the poor and extensive metabolizers
• extensive metaboliser–these subjects have normal CYP2D6 function
• ultrarapid metaboliser–these subjects have multiple copies of the CYP2D6 gene
  Gene
  A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
  
   expressed, and therefore greater-than-normal CYP2D6 function

A patient's CYP2D6 phenotype is often clinically determined via the administration of debrisoquine

Debrisoquine

Debrisoquine is a derivative of guanidine. It is an antihypertensive drug similar to guanethidine. Debrisoquine is frequently used for phenotyping the CYP2D6 enzyme, a drug metabolizing enzyme....

 (a selective CYP2D6 substrate) and subsequent plasma concentration assay of the debrisoquine metabolite

Metabolite

Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. A primary metabolite is directly involved in normal growth, development, and reproduction. Alcohol is an example of a primary metabolite produced in large-scale by industrial...

 (4-hydroxydebrisoquine). More recently, a "DNA microarray

DNA microarray

A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...

" has been developed, known as the AmpliChip

AmpliChip CYP450 Test

AmpliChip CYP450 Test is a clinical test from Roche. The test aims to find the specific gene types of the patient that will determine how he or she metabolizes certain medicines, therefore guides the doctors to prescribe medicine for best effectiveness and least side effects.The AmpliChip CYP450...

, which allows the automated determination of a patient's CYP2D6 (and CYP2C19

CYP2C19

Cytochrome P450 2C19 , a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several...

) genotype.

CYP2D6 activity was tested in "healthy infants receiving an oral dose (0.3 mg/kg) of dextromethorphan

Dextromethorphan

Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...

 (DM) at 0.5, 1, 2, 4, 6, and 12 months of age. DM and its major metabolites were measured in urine. CYP2D6 genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. Genotyping data indicated a strong correlation between CYP2D6 genotype and DM O-demethylation (beta=-0.638; 95% CI: -0.745, -0.532; P<0.001). CYP2D6 activity was detectable and concordant with genotype by 2 weeks of age, showed no relationship with gestational age, and did not change with post natal age up to 1 year. In contrast, DM N-demethylation developed significantly more slowly over the first year of life. Genotype and the temporal acquisition of drug biotransformation are critical determinants of a drug response in infants."

Genetic basis of variability

The genetic basis for extensive and poor metaboliser variability is the CYP2D6 allele

Allele

An allele is one of two or more forms of a gene or a genetic locus . "Allel" is an abbreviation of allelomorph. Sometimes, different alleles can result in different observable phenotypic traits, such as different pigmentation...

, located on chromosome 22. Subjects possessing certain allelic variants will show normal, decreased, or no CYP2D6 function, depending on the allele.

CYP2D6 allele and enzyme activity
Allele	CYP2D6 activity
CYP2D6*1	normal
CYP2D6*2	increased
CYP2D6*3	none
CYP2D6*4	none
CYP2D6*5	none
CYP2D6*9	decreased
CYP2D6*10	decreased
CYP2D6*17	decreased

Ethnic factors in variability

Ethnicity is a factor in the occurrence of CYP2D6 variability. The prevalence of CYP2D6 poor metabolizers is approximately 6–10% in white

White people

White people is a term which usually refers to human beings characterized, at least in part, by the light pigmentation of their skin...

 populations, but is lower in most other ethnic groups such as Asians

Asian people

Asian people or Asiatic people is a term with multiple meanings that refers to people who descend from a portion of Asia's population.- Central Asia :...

 (2%). In blacks

Black people

The term black people is used in systems of racial classification for humans of a dark skinned phenotype, relative to other racial groups.Different societies apply different criteria regarding who is classified as "black", and often social variables such as class, socio-economic status also plays a...

, the frequency of poor metabolizers is greater than for whites. The occurrence of CYP2D6 ultrarapid metabolisers appears to be greater among Middle East

Middle East

The Middle East is a region that encompasses Western Asia and Northern Africa. It is often used as a synonym for Near East, in opposition to Far East...

ern and North Africa

North Africa

North Africa or Northern Africa is the northernmost region of the African continent, linked by the Sahara to Sub-Saharan Africa. Geopolitically, the United Nations definition of Northern Africa includes eight countries or territories; Algeria, Egypt, Libya, Morocco, South Sudan, Sudan, Tunisia, and...

n populations.

This variability is accounted for by the differences in the prevalence of various CYP2D6 alleles among the populations–approximately 10% of whites appear to have the non-functional CYP2D6*4 allele, while approximately 50% of Asians possess the CYP2D6*10 allele, which should produce decreased CYP2D6 function; however this still appears to be within the normal range and are still grouped as intermediate metabolisers.

CYP2D6 ligands

Following is a table of selected substrates, inducers

Enzyme induction and inhibition

Enzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...

 and inhibitors

Enzyme induction and inhibition

Enzyme induction is a process in which a molecule induces the expression of an enzyme.Enzyme inhibition can refer to* the inhibition of the expression of the enzyme by another molecule...

 of CYP2D6. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2D6 can be classified by their potency

Potency (pharmacology)

In the field of pharmacology, potency is a measure of drug activity expressed in terms of the amount required to produce an effect of given intensity. A highly potent drug evokes a larger response at low concentrations, while a drug of lower potency evokes a small response at low concentrations...

, such as:

• Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance
  Clearance (medicine)
  In medicine, the clearance is a measurement of the renal excretion ability. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics...
  
  .
• Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
• Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.

Selected inducers, inhibitors and substrates of CYP2D6

Substrates ↑ = bioactivation by CYP2D6	Inhibitors	Inducers
All tricyclic antidepressants, e.g. imipramine Imipramine Imipramine , also known as melipramine, is an antidepressant medication, a tricyclic antidepressant of the dibenzazepine group... amitriptyline Amitriptyline Amitriptyline is a tricyclic antidepressant . It is the most widely used TCA and has at least equal efficacy against depression as the newer class of SSRIs... etc. Most SSRIs (antidepressant), e.g. fluoxetine Fluoxetine Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company... paroxetine Paroxetine Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline... fluvoxamine Fluvoxamine Fluvoxamine is an antidepressant which functions as a selective serotonin reuptake inhibitor . Fluvoxamine was first approved by the U.S. Food and Drug Administration in 1993 for the treatment of obsessive compulsive disorder . Fluvoxamine CR is approved to treat social anxiety disorder... venlafaxine Venlafaxine Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...  (SNRI Serotonin-norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...  antidepressant) mianserin Mianserin Mianserin is a psychoactive drug of the tetracyclic antidepressant chemical class which is classified as a noradrenergic and specific serotonergic antidepressant and has antidepressant, anxiolytic, hypnotic, antiemetic, orexigenic, and antihistamine effects...  (tetracyclic antidepressant Tetracyclic antidepressant Tetracyclic antidepressants are a class of drugs used primarily as antidepressants that were first introduced in the 1970s. They are named after their chemical structure which contains four rings of atoms and are closely related to the tricyclic antidepressants which contain three rings of... ) opioids codeine Codeine Codeine or 3-methylmorphine is an opiate used for its analgesic, antitussive, and antidiarrheal properties...  ↑ tramadol Tramadol Tramadol hydrochloride is a centrally acting synthetic opioid analgesic used in treating moderate pain. The drug has a wide range of applications, including treatment for restless legs syndrome and fibromyalgia...  ↑ oxycodone Oxycodone Oxycodone is an opioid analgesic medication synthesized from opium-derived thebaine. It was developed in 1916 in Germany, as one of several new semi-synthetic opioids in an attempt to improve on the existing opioids: morphine, diacetylmorphine , and codeine.Oxycodone oral medications are generally... antipsychotics, e.g. haloperidol Haloperidol Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines.... risperidone Risperidone Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism... perphenazine Perphenazine Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades.... thioridazine Thioridazine Thioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis... zuclopenthixol Zuclopenthixol Zuclopenthixol , also known as zuclopentixol, is a typical antipsychotic drug of the thioxanthene class... aripiprazole Aripiprazole Aripiprazole is an atypical antipsychotic and antidepressant used in the treatment of schizophrenia, bipolar disorder, and clinical depression... chlorpromazine Chlorpromazine Chlorpromazine is a typical antipsychotic... levomepromazine Levomepromazine Levomepromazine in Germany and Methotrimeprazine in America is an aliphatic phenothiazine neuroleptic drug... remoxipride Remoxipride Remoxipride is an atypical antipsychotic which was previously used in Europe for the treatment of schizophrenia but was withdrawn due to toxicity concerns . It was initially launched by AstraZeneca in 1990 and suspension of its use began in 1993... minaprine Minaprine Minaprine is an antidepressant used in France for the treatment of depression. It acts as a reversible inhibitor of MAO-A . It has also been found to inhibit acetylcholinesterase.- References :...  (RIMA antidepressant) tamoxifen Tamoxifen Tamoxifen is an antagonist of the estrogen receptor in breast tissue via its active metabolite, hydroxytamoxifen. In other tissues such as the endometrium, it behaves as an agonist, hence tamoxifen may be characterized as a mixed agonist/antagonist...  ↑ (SERM Selective estrogen receptor modulator Selective Estrogen Receptor Modulators are a class of compounds that act on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively... ) beta-blockers metoprolol Metoprolol Metoprolol is a selective β1 receptor blocker used in treatment of several diseases of the cardiovascular system, especially hypertension. The active substance metoprolol is employed either as metoprolol succinate or metoprolol tartrate... timolol Timolol Timolol maleate is a non-selective beta-adrenergic receptor blocker.-Uses:In its oral form , it is used:* to treat high blood pressure* to prevent heart attacks* to prevent migraine headaches... alprenolol Alprenolol Alprenolol, or alfeprol, alpheprol, and alprenololum , is a non-selective beta blocker as well as 5-HT1A receptor antagonist, used in the treatment of angina pectoris... carvedilol Carvedilol Carvedilol is a non-selective beta blocker/alpha-1 blocker indicated in the treatment of mild to moderate congestive heart failure . It is marketed under various trade names including Carvil , Coreg , Dilatrend , Eucardic , and Carloc as a generic drug ., and as a... bufuralol Bufuralol Bufuralol is a potent beta-adrenoceptor antagonist with partial agonist activity. It is metabolized by CYP2D6.... nebivolol Nebivolol Nebivolol is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and, in Europe, also for left ventricular failure... propranolol debrisoquine Debrisoquine Debrisoquine is a derivative of guanidine. It is an antihypertensive drug similar to guanethidine. Debrisoquine is frequently used for phenotyping the CYP2D6 enzyme, a drug metabolizing enzyme....  (antihypertensive Antihypertensive The antihypertensives are a class of drugs that are used to treat hypertension . Evidence suggests that reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from... ) Class I antiarrhythmics flecainide Flecainide Flecainide acetate is a class Ic antiarrhythmic agent used to prevent and treat tachyarrhythmias . It is used to treat a variety of cardiac arrhythmias including paroxysmal atrial fibrillation , paroxysmal supraventricular tachycardia Flecainide acetate is a class Ic antiarrhythmic agent used to... propafenone Propafenone Propafenone is a class Ic anti-arrhythmic medication, which treats illnesses associated with rapid heart beats such as atrial and ventricular arrhythmias.-Mechanism of action:... encainide Encainide Encainide is a class Ic antiarrhythmic agent. It is no longer used because its frequent proarrhythmic side effects.... mexiletine Mexiletine Mexiletine belongs to the Class IB anti-arrhythmic group of medicines. It is used to treat arrhythmias within the heart, or seriously irregular heartbeats. It slows conduction in the heart and makes the heart tissue less sensitive. Dizziness, heartburn, nausea, nervousness, trembling, unsteadiness... lidocaine Lidocaine Lidocaine , Xylocaine, or lignocaine is a common local anesthetic and antiarrhythmic drug. Lidocaine is used topically to relieve itching, burning and pain from skin inflammations, injected as a dental anesthetic or as a local anesthetic for minor surgery.- History :Lidocaine, the first amino... sparteine Sparteine Sparteine is a class 1a antiarrhythmic agent; a sodium channel blocker. It is an alkaloid and can be extracted from scotch broom. It is the predominant alkaloid in Lupinus mutabilis, and is thought to chelate the bivalents calcium and magnesium... ondansetron Ondansetron Ondansetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic , often following chemotherapy. Its effects are thought to be on both peripheral and central nerves...  (antiemetic Antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer.... ) donepezil Donepezil Donepezil, marketed under the trade name Aricept by its developer Eisai and partner Pfizer, is a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the palliative treatment of mild to moderate Alzheimer's disease. Common side effects include...  (acetylcholinesterase inhibitor Acetylcholinesterase inhibitor An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, increasing both the level and duration of action of the neurotransmitter acetylcholine.- Uses :Acetylcholinesterase inhibitors:* Occur naturally as... ) phenformin Phenformin Phenformin is an anti-diabetic drug from the biguanide class. It was marketed as DBI by Ciba-Geigy but was withdrawn from most markets in the late 1970s due to a high risk of lactic acidosis, which was fatal in 50% of cases....  (antidiabetic) tropisetron Tropisetron Tropisetron is a serotonin 5-HT3 receptor antagonist used mainly as an antiemetic to treat nausea and vomiting following chemotherapy, although it has been used experimentally as an analgesic in cases of fibromyalgia. The drug is available in a 5 mg oral preparation or in 2 mg...  (5-HT3 receptor antagonist) amphetamine Amphetamine Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...  (in ADHD Attention-deficit hyperactivity disorder Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and... , narcolepsy Narcolepsy Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia... ) atomoxetine (in ADHD Attention-deficit hyperactivity disorder Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and... ) chlorphenamine Chlorphenamine Chlorphenamine or chlorpheniramine , commonly marketed in the form of chlorpheniramine maleate , is a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. Its sedative effects are relatively weak compared to other...  (antihistamine Antihistamine An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions... ) dexfenfluramine Dexfenfluramine Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain...  (serotoninergic Serotonin Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...  anorectic Anorectic An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The... ) dextromethorphan Dextromethorphan Dextromethorphan is an antitussive drug. It is one of the active ingredients in many over-the-counter cold and cough medicines, such as Robitussin, NyQuil, Dimetapp, Vicks, Coricidin, Delsym, and others, including generic labels. Dextromethorphan has also found other uses in medicine, ranging...  (antitussive) duloxetine Duloxetine Duloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...  (SNRI Serotonin-norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders... ) metoclopramide Metoclopramide Metoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...  (dopamine antagonist Dopamine antagonist A dopamine antagonist is a drug which blocks dopamine receptors by receptor antagonism. There are five known types of dopamine receptors in the human body; they are found in the brain, peripheral nervous system, blood vessels, gastrointestinal tract and the kidney.-Uses and examples:* Used as... ) Methoxyamphetamine perhexiline Perhexiline Perhexiline is a prophylactic antianginal agent used primarily in Australia and New Zealand. Perhexiline is thought to act by inhibiting mitochondrial carnitine palmitoyltransferase-1. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production...   (antianginal agent) phenacetin Phenacetin Phenacetin is an analgesic, once widely used; its use has declined because of its adverse effects.-History:Phenacetin was introduced in 1887, and was used principally as an analgesic, and was one of the first synthetic fever reducers to go on the market...   (analgesic Analgesic An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos .... ) promethazine Promethazine Promethazine is a first-generation antihistamine of the phenothiazine family. The drug has anti-motion sickness, antiemetic, and anticholinergic effects, as well as a strong sedative effect and in some countries is prescribed for insomnia when benzodiazepines are contraindicated...  (antihistamine Antihistamine An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...  antiemetic Antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer.... )	strong: SSRI Selective serotonin reuptake inhibitor Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed... s fluoxetine Fluoxetine Fluoxetine is an antidepressant of the selective serotonin reuptake inhibitor class. It is manufactured and marketed by Eli Lilly and Company... paroxetine Paroxetine Paroxetine is an SSRI antidepressant. Marketing of the drug began in 1992 by the pharmaceutical company SmithKline Beecham, now GlaxoSmithKline... bupropion Bupropion Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...  (non-SSRI antidepressant) quinidine Quinidine Quinidine is a pharmaceutical agent that acts as a class I antiarrhythmic agent in the heart. It is a stereoisomer of quinine, originally derived from the bark of the cinchona tree.-Mechanism:...  (class I antiarrhythmic agent) cinacalcet Cinacalcet Cinacalcet is a drug that acts as a calcimimetic by allosteric activation of the calcium-sensing receptor that is expressed in various human organ tissues. It is sold by Amgen under the trade name Sensipar in North America and Australia and as Mimpara in Europe...  (calcimimetic) ritonavir Ritonavir Ritonavir, with trade name Norvir , is an antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS....  (antiretroviral) Moderate sertraline Sertraline Sertraline hydrochloride is an antidepressant of the selective serotonin reuptake inhibitor class. It was introduced to the market by Pfizer in 1991. Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive–compulsive, panic, and social anxiety disorders in...  (SSRI Selective serotonin reuptake inhibitor Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed... ) duloxetine Duloxetine Duloxetine is a serotonin-norepinephrine reuptake inhibitor manufactured and marketed by Eli Lilly. It is effective for major depressive disorder and has been shown to be as effective as venlafaxine for generalized anxiety disorder...  (SNRI Serotonin-norepinephrine reuptake inhibitor Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders... terbinafine Terbinafine Terbinafine hydrochloride is a...  (antifungal) weak: buprenorphine Buprenorphine Buprenorphine is a semi-synthetic opioid that is used...  (in opioid addiction) amiodarone Amiodarone Amiodarone is an antiarrhythmic agent used for various types of tachyarrhythmias , both ventricular and supraventricular arrhythmias. Discovered in 1961, it was not approved for use in the United States until 1985...  (antiarrhythmic) cimetidine Cimetidine Cimetidine INN is a histamine H2-receptor antagonist that inhibits the production of acid in the stomach. It is largely used in the treatment of heartburn and peptic ulcers. It is marketed by GlaxoSmithKline under the trade name Tagamet...  (H2-receptor antagonist H2-receptor antagonist The H2 receptor antagonists are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective ... ) unspecified potency: antipsychotic Antipsychotic An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s... s haloperidol Haloperidol Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines.... perphenazine Perphenazine Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades.... thioridazine Thioridazine Thioridazine is a piperidine typical antipsychotic drug belonging to the phenothiazine drug group and was previously widely used in the treatment of schizophrenia and psychosis... zuclopenthixol Zuclopenthixol Zuclopenthixol , also known as zuclopentixol, is a typical antipsychotic drug of the thioxanthene class... risperidone Risperidone Risperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism... chlorpromazine Chlorpromazine Chlorpromazine is a typical antipsychotic... hyperforin Hyperforin Hyperforin is a phytochemical produced by some of the members of the plant genus Hypericum, notably Hypericum perforatum .- Occurrence :...  (St. Johns Wort) antihistamine Antihistamine An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions... s (H1-receptor antagonists) Promethazine Promethazine Promethazine is a first-generation antihistamine of the phenothiazine family. The drug has anti-motion sickness, antiemetic, and anticholinergic effects, as well as a strong sedative effect and in some countries is prescribed for insomnia when benzodiazepines are contraindicated... chlorphenamine Chlorphenamine Chlorphenamine or chlorpheniramine , commonly marketed in the form of chlorpheniramine maleate , is a first-generation alkylamine antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. Its sedative effects are relatively weak compared to other... diphenhydramine Diphenhydramine Diphenhydramine hydrochloride is a first-generation antihistamine possessing anticholinergic, antitussive, antiemetic, and sedative properties which is mainly used to treat allergies. Like most other first-generation antihistamines, the drug also has a powerful hypnotic effect, and for this reason... hydroxyzine Hydroxyzine Hydroxyzine is a first-generation antihistamine of the diphenylmethane and piperazine classes. It was first synthesized by Union Chimique Belge in 1956 and was marketed by Pfizer in the United States later the same year, and is still in widespread use today.... tripelennamine Tripelennamine Tripelennamine is psychoactive drug and member of the pyridine and ethylenediamine classes that is used as an antipruritic and first-generation antihistamine... some SSRI Selective serotonin reuptake inhibitor Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. The efficacy of SSRIs is disputed...  antidepressants citalopram Citalopram Citalopram brand names: Celexa, Cipramil) is an antidepressant drug of the selective serotonin reuptake inhibitor class. It has U.S... escitalopram Escitalopram Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor class. It is approved by the U.S... clemastine Clemastine Clemastine, also known as meclastin, is an antihistamine and anticholinergic. Unlike loratadine or fexofenadine, clemastine is a sedating antihistamine, however it exhibits fewer other side effects than most of the widely used antihistamines. Clemastine is also classified as an antipruritic...   (antihistamine Antihistamine An H1 antagonist is a histamine antagonist of the H1 receptor that serves to reduce or eliminate effects mediated by histamine, an endogenous chemical mediator released during allergic reactions...  and anticholinergic Anticholinergic An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine.... ) celecoxib Celecoxib Celecoxib INN is a sulfa non-steroidal anti-inflammatory drug and selective COX-2 inhibitor used in the treatment of osteoarthritis, rheumatoid arthritis, acute pain, painful menstruation and menstrual symptoms, and to reduce numbers of colon and rectum polyps in patients with familial...  (NSAID) clomipramine Clomipramine Clomipramine is a tricyclic antidepressant . It was developed in the 1960s by the Swiss drug manufacturer Geigy and has been in clinical use worldwide ever since.- Indications :...  (tricyclic antidepressant Tricyclic antidepressant Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms... ) cocaine Cocaine Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...  (stimulant Stimulant Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others... ) doxorubicin Doxorubicin Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....  (chemotherapeutic) metoclopramide Metoclopramide Metoclopramide is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.-Medical uses:Metoclopramide is commonly...  (antiemetic Antiemetic An antiemetic is a drug that is effective against vomiting and nausea. Antiemetics are typically used to treat motion sickness and the side effects of opioid analgesics, general anaesthetics, and chemotherapy directed against cancer.... , prokinetic) methadone Methadone Methadone is a synthetic opioid, used medically as an analgesic and a maintenance anti-addictive for use in patients with opioid dependency. It was developed in Germany in 1937...  (analgesic Analgesic An analgesic is any member of the group of drugs used to relieve pain . The word analgesic derives from Greek an- and algos ....  and anti-addictive) moclobemide Moclobemide Moclobemide is a monoamine oxidase inhibitor drug primarily used to treat depression and social anxiety. Although clinical trials with the medicine began in 1977, it is not approved for use in the United States...  (antidepressant Antidepressant An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;... ) ranitidine Ranitidine Ranitidine is a histamine H2-receptor antagonist that inhibits stomach acid production. It is commonly used in treatment of peptic ulcer disease and gastroesophageal reflux disease . Ranitidine is also used alongside fexofenadine and other antihistamines for the treatment of skin conditions...  (H2-receptor antagonist H2-receptor antagonist The H2 receptor antagonists are a class of drugs used to block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonists are used in the treatment of dyspepsia, although they have been surpassed in popularity by the more effective ... ) doxepin Doxepin Doxepin is a psychotropic agent with tricyclic antidepressant and anxiolytic properties, known under many brand-names such as Aponal, the original preparation by Boehringer-Mannheim, now part of the Roche group; Adapine, Doxal , Deptran, Sinquan and Sinequan...  (tricyclic antidepressant Tricyclic antidepressant Tricyclic antidepressants are heterocyclic chemical compounds used primarily as antidepressants. The TCAs were first discovered in the early 1950s and were subsequently introduced later in the decade; they are named after their chemical structure, which contains three rings of atoms... , anxiolytic Anxiolytic An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms... ) halofantrine Halofantrine Halofantrine is a drug used to treat malaria. Halofantrine's structure contains a substituted phenanthrene, and is related to the antimalarial drugs quinine and lumefantrine. Marketed as Halfan, halofantrine is never used to prevent malaria and its mode of action is unknown...  (in malaria Malaria Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases... ) levomepromazine Levomepromazine Levomepromazine in Germany and Methotrimeprazine in America is an aliphatic phenothiazine neuroleptic drug...  (antipsychotic Antipsychotic An antipsychotic is a tranquilizing psychiatric medication primarily used to manage psychosis , particularly in schizophrenia and bipolar disorder. A first generation of antipsychotics, known as typical antipsychotics, was discovered in the 1950s... ) mibefradil Mibefradil Mibefradil is a drug for the treatment of hypertension and chronic angina pectoris. It belongs to a group known as calcium channel blockers.It is nonselective....  (calcium channel blocker Calcium channel blocker A calcium channel blocker is a chemical that disrupts the movement of calcium through calcium channels.CCB drugs devised to target neurons are used as antiepileptics. However, the most widespread clinical usage of calcium channel blockers is to decrease blood pressure in patients with... ) midodrine Midodrine Midodrine is a vasopressor/antihypotensive agent. Midodrine was approved in the United States by the Food and Drug Administration in 1996 for the treatment of orthostatic hypotension...  (α1 agonist) ticlopidine Ticlopidine Ticlopidine is an antiplatelet drug in the thienopyridine family. Like clopidogrel, it is an adenosine diphosphate receptor inhibitor. It is used in patients in whom aspirin is not tolerated, or in whom dual antiplatelet therapy is desirable...  (antiplatelet Antiplatelet drug An antiplatelet drug is a member of a class of pharmaceuticals that decrease platelet aggregation and inhibit thrombus formation... )	dexamethasone Dexamethasone Dexamethasone is a potent synthetic member of the glucocorticoid class of steroid drugs. It acts as an anti-inflammatory and immunosuppressant...  (glucocorticoid Glucocorticoid Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell... ) rifampicin Rifampicin Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...  (bactericidal)

External links

• Flockhart Lab Cyp2D6 Substrates Page at IUPUI
  Indiana University-Purdue University Indianapolis
  Indiana University – Purdue University Indianapolis is an urban campus of Indiana University and Purdue University in Indianapolis, Indiana, United States. Indiana University is the managing partner...
  
  
• PharmGKB: Annotated PGx Gene Information for CYP2D6