Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index

DrugDrug NameDrug Indication
DB00321AmitriptylineThis drug in indicated for the following conditions [FDA label]: Major depressive disorder in adults Management of neuropathic pain in adults Prophylactic treatment of chronic tension-type headache (CTTH) in adults Prophylactic treatment of migraine in adults Treatment of nocturnal enuresis in children aged 6 years and above when organic pathology, including spina bifida and related disorders, have been excluded and no response has been achieved to all other non-drug and drug treatments, including antispasmodics and vasopressin-related products. This product should only be prescribed by a healthcare professional with expertise in the management of persistent enuresis [FDA label] Off-label uses: irritable bowel syndrome, sleep disorders, diabetic neuropathy, agitation, fibromyalgia, and insomnia
DB01242ClomipramineMay be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder). Unlabeled indications include: depression, panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy (limited evidence), autistic disorder (limited evidence), trichotillomania (limited evidence), onchophagia (limited evidence), stuttering (limited evidence), premature ejaculation, and premenstrual syndrome.
DB01151DesipramineFor relief of symptoms in various depressive syndromes, especially endogenous depression. It has also been used to manage chronic peripheral neuropathic pain, as a second line agent for the management of anxiety disorders (e.g. panic disorder, generalized anxiety disorder), and as a second or third line agent in the ADHD management.
DB09167DosulepinIndicated in the treatment of symptoms of depressive illness, especially where an anti-anxiety effect is required.
DB00458ImipramineFor the relief of symptoms of depression and as temporary adjunctive therapy in reducing enuresis in children aged 6 years and older [FDA Label]. May also be used off-label to manage panic disorders with or without agoraphobia, as a second line agent for ADHD in children and adolescents, to manage bulimia nervosa, for short-term management of acute depressive episodes in bipolar disorder and schizophrenia, for the treatment of acute stress disorder and posttraumatic stress disorder, and for symptomatic treatment of postherpetic neuralgia and painful diabetic neuropathy [L1349,L1348,A31900,L1351,L1352,L1353,A31904].
DB13411LofepramineNot Available
DB13384MelitracenNot Available
DB00540NortriptylinePrimarily indicated for the relief of symptoms of depression.
DB00454MeperidineUsed to control moderate to severe pain.
DB00726TrimipramineFor the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance
DB11823EsketamineThis drug is indicated in conjunction with an oral antidepressant for the treatment of treatment-resistant depression (TRD) in adults [FDA label]. Note: Esketamine is not approved as an anesthetic agent. The safety and effectiveness of esketamine as an anesthetic agent have not been established to this date [FDA label].
DrugDrug NameTargetType
DB00321AmitriptylineSodium-dependent serotonin transportertarget
DB00321AmitriptylineSodium-dependent noradrenaline transportertarget
DB00321AmitriptylinePotassium voltage-gated channel subfamily KQT member 2target
DB00321AmitriptylineAlpha-2A adrenergic receptortarget
DB00321AmitriptylineCytochrome P450 1A2enzyme
DB00321AmitriptylineCytochrome P450 2C19enzyme
DB00321AmitriptylineCytochrome P450 2D6enzyme
DB00321AmitriptylineSerum albumincarrier
DB00321AmitriptylineAlpha-1-acid glycoprotein 1carrier
DB00321AmitriptylineHistamine H1 receptortarget
DB00321Amitriptyline5-hydroxytryptamine receptor 2Atarget
DB00321Amitriptyline5-hydroxytryptamine receptor 1Atarget
DB00321AmitriptylineAlpha-1A adrenergic receptortarget
DB00321AmitriptylineCytochrome P450 3A4enzyme
DB00321AmitriptylineCytochrome P450 3A5enzyme
DB00321AmitriptylinePotassium voltage-gated channel subfamily A member 1target
DB00321AmitriptylineAlpha-1D adrenergic receptortarget
DB00321AmitriptylineDelta-type opioid receptortarget
DB00321AmitriptylineKappa-type opioid receptortarget
DB00321AmitriptylineHigh affinity nerve growth factor receptortarget
DB00321AmitriptylineBDNF/NT-3 growth factors receptortarget
DB00321AmitriptylineCytochrome P450 2C9enzyme
DB00321AmitriptylineCytochrome P450 2B6enzyme
DB00321AmitriptylineCytochrome P450 2C8enzyme
DB00321AmitriptylineHistamine H2 receptortarget
DB00321AmitriptylineHistamine H4 receptortarget
DB00321AmitriptylineSigma non-opioid intracellular receptor 1target
DB00321Amitriptyline5-hydroxytryptamine receptor 2Ctarget
DB00321AmitriptylineAlpha-1B adrenergic receptortarget
DB00321Amitriptyline5-hydroxytryptamine receptor 7target
DB00321Amitriptyline5-hydroxytryptamine receptor 1Dtarget
DB00321AmitriptylineMu-type opioid receptortarget
DB00321Amitriptyline5-hydroxytryptamine receptor 1Btarget
DB00321Amitriptyline5-hydroxytryptamine receptor 6target
DB00321AmitriptylinePotassium voltage-gated channel subfamily KQT member 3target
DB00321AmitriptylineUDP-glucuronosyltransferase 1-1enzyme
DB00321Amitriptyline5-hydroxytryptamine receptor 1Ctarget
DB00321AmitriptylineMuscarinic acetylcholine receptortarget
DB00321AmitriptylineHERG human cardiac K+ channeltarget
DB00321AmitriptylineMultidrug resistance protein 1transporter
DB01242ClomipramineSodium-dependent serotonin transportertarget
DB01242ClomipramineSodium-dependent noradrenaline transportertarget
DB01242ClomipramineGlutathione S-transferase Ptarget
DB01242Clomipramine5-hydroxytryptamine receptor 2Atarget
DB01242ClomipramineCytochrome P450 1A2enzyme
DB01242ClomipramineCytochrome P450 2D6enzyme
DB01242ClomipramineCytochrome P450 2C19enzyme
DB01242ClomipramineMultidrug resistance protein 1transporter
DB01242ClomipramineCytochrome P450 3A4enzyme
DB01242Clomipramine5-hydroxytryptamine receptor 2Btarget
DB01242Clomipramine5-hydroxytryptamine receptor 2Ctarget
DB01242ClomipramineSerum albumincarrier
DB01151DesipramineMuscarinic acetylcholine receptor M1target
DB01151DesipramineSodium-dependent noradrenaline transportertarget
DB01151DesipramineBeta-2 adrenergic receptortarget
DB01151DesipramineMuscarinic acetylcholine receptor M2target
DB01151DesipramineSodium-dependent serotonin transportertarget
DB01151DesipramineHistamine H1 receptortarget
DB01151DesipramineBeta-1 adrenergic receptortarget
DB01151DesipramineCytochrome P450 2D6enzyme
DB01151DesipramineMuscarinic acetylcholine receptor M3target
DB01151DesipramineMuscarinic acetylcholine receptor M4target
DB01151DesipramineMuscarinic acetylcholine receptor M5target
DB01151DesipramineAlpha-1 adrenergic receptorstarget
DB01151Desipramine5-hydroxytryptamine receptor 2Atarget
DB01151DesipramineAlpha-1-acid glycoprotein 1carrier
DB01151DesipramineCytochrome P450 2B6enzyme
DB01151DesipramineCytochrome P450 3A4enzyme
DB01151DesipramineSolute carrier family 22 member 2transporter
DB01151DesipramineSolute carrier family 22 member 1transporter
DB01151DesipramineSolute carrier family 22 member 3transporter
DB01151DesipramineSolute carrier family 22 member 5transporter
DB01151DesipramineMultidrug resistance protein 1transporter
DB01151DesipramineSolute carrier family 22 member 4transporter
DB01151DesipramineCytochrome P450 1A2enzyme
DB01151DesipramineCytochrome P450 2A6enzyme
DB01151DesipramineCytochrome P450 2C18enzyme
DB01151DesipramineCytochrome P450 2C19enzyme
DB01151DesipramineCytochrome P450 2E1enzyme
DB01151DesipramineSphingomyelin phosphodiesterasetarget
DB01151Desipramine5-hydroxytryptamine receptor 1Atarget
DB01151Desipramine5-hydroxytryptamine receptor 2Ctarget
DB01151DesipramineD(2) dopamine receptortarget
DB01151DesipramineAlpha-2 adrenergic receptorstarget
DB09167Dosulepin5-hydroxytryptamine receptor 1Atarget
DB09167Dosulepin5-hydroxytryptamine receptor 2Atarget
DB09167DosulepinCytochrome P450 2D6enzyme
DB09167DosulepinCytochrome P450 1A2enzyme
DB09167DosulepinCytochrome P450 2C19enzyme
DB09167DosulepinCytochrome P450 2C9enzyme
DB09167DosulepinHistamine H1 receptortarget
DB09167DosulepinMuscarinic acetylcholine receptor M1target
DB09167DosulepinMuscarinic acetylcholine receptor M2target
DB09167DosulepinMuscarinic acetylcholine receptor M3target
DB09167DosulepinMuscarinic acetylcholine receptor M4target
DB09167DosulepinMuscarinic acetylcholine receptor M5target
DB09167DosulepinSodium-dependent noradrenaline transportertarget
DB09167DosulepinSodium-dependent serotonin transportertarget
DB09167DosulepinAlpha-1 adrenergic receptorstarget
DB09167DosulepinAlpha-2 adrenergic receptorstarget
DB00458ImipramineSodium-dependent noradrenaline transportertarget
DB00458ImipramineSodium-dependent serotonin transportertarget
DB00458ImipramineCytochrome P450 1A2enzyme
DB00458ImipramineCytochrome P450 2C19enzyme
DB00458ImipramineCytochrome P450 2D6enzyme
DB00458ImipramineHistamine H1 receptortarget
DB00458ImipramineAlpha-1A adrenergic receptortarget
DB00458Imipramine5-hydroxytryptamine receptor 2Atarget
DB00458ImipramineMuscarinic acetylcholine receptor M1target
DB00458ImipramineMuscarinic acetylcholine receptor M2target
DB00458ImipramineMuscarinic acetylcholine receptor M3target
DB00458ImipramineMuscarinic acetylcholine receptor M4target
DB00458ImipramineMuscarinic acetylcholine receptor M5target
DB00458ImipraminePotassium voltage-gated channel subfamily D member 2target
DB00458ImipraminePotassium voltage-gated channel subfamily D member 3target
DB00458ImipramineAlpha-1D adrenergic receptortarget
DB00458ImipramineAlpha-1-acid glycoprotein 1carrier
DB00458ImipramineSolute carrier family 22 member 2transporter
DB00458ImipramineSolute carrier family 22 member 3transporter
DB00458ImipramineMultidrug resistance protein 1transporter
DB00458ImipramineSolute carrier family 22 member 4transporter
DB00458ImipramineCytochrome P450 3A4enzyme
DB00458ImipramineCytochrome P450 2B6enzyme
DB00458ImipramineCytochrome P450 2C18enzyme
DB00458ImipramineCytochrome P450 2E1enzyme
DB00458ImipramineCytochrome P450 3A7enzyme
DB00458Imipramine5-hydroxytryptamine receptor 2Ctarget
DB00458ImipramineAlpha-1B adrenergic receptortarget
DB00458Imipramine5-hydroxytryptamine receptor 7target
DB00458ImipramineD(1) dopamine receptortarget
DB00458ImipramineD(2) dopamine receptortarget
DB00458ImipraminePotassium voltage-gated channel subfamily H member 2target
DB00458ImipramineSodium-dependent dopamine transportertarget
DB00458Imipramine5-hydroxytryptamine receptor 1Atarget
DB00458Imipramine5-hydroxytryptamine receptor 6target
DB00458ImipraminePotassium voltage-gated channel subfamily H member 1target
DB00458ImipramineSerum albumincarrier
DB00458ImipramineAlpha-1-acid glycoprotein 2target
DB00540NortriptylineSodium-dependent serotonin transportertarget
DB00540NortriptylineSodium-dependent noradrenaline transportertarget
DB00540NortriptylineCytochrome P450 1A2enzyme
DB00540NortriptylineCytochrome P450 2D6enzyme
DB00540NortriptylineSerum albumincarrier
DB00540NortriptylineAlpha-1-acid glycoprotein 1carrier
DB00540NortriptylineHistamine H1 receptortarget
DB00540NortriptylineMuscarinic acetylcholine receptor M1target
DB00540NortriptylineMuscarinic acetylcholine receptor M2target
DB00540NortriptylineMuscarinic acetylcholine receptor M3target
DB00540NortriptylineMuscarinic acetylcholine receptor M4target
DB00540NortriptylineMuscarinic acetylcholine receptor M5target
DB00540Nortriptyline5-hydroxytryptamine receptor 2Atarget
DB00540NortriptylineAlpha-1A adrenergic receptortarget
DB00540Nortriptyline5-hydroxytryptamine receptor 1Atarget
DB00540NortriptylineCytochrome P450 3A4enzyme
DB00540NortriptylineCytochrome P450 3A5enzyme
DB00540NortriptylineAlpha-1D adrenergic receptortarget
DB00540NortriptylineCytochrome P450 2C19enzyme
DB00540NortriptylineProstaglandin G/H synthase 1enzyme
DB00540NortriptylineCytochrome P450 2E1enzyme
DB00540Nortriptyline5-hydroxytryptamine receptor 2Ctarget
DB00540Nortriptyline5-hydroxytryptamine receptor 6target
DB00540NortriptylineAlpha-1B adrenergic receptortarget
DB00540NortriptylineAlpha-2 adrenergic receptorstarget
DB00540NortriptylineBeta adrenergic receptortarget
DB00540NortriptylineD(2) dopamine receptortarget
DB00540NortriptylineSigma receptortarget
DB00540Nortriptyline5-hydroxytryptamine receptor 1Ctarget
DB00454MeperidineKappa-type opioid receptortarget
DB00454MeperidineCytochrome P450 2D6enzyme
DB00454MeperidineCytochrome P450 2B6enzyme
DB00454MeperidineGlutamate receptor ionotropic, NMDA 1target
DB00454MeperidineGlutamate receptor ionotropic, NMDA 2Btarget
DB00454MeperidineGlutamate receptor ionotropic, NMDA 2Atarget
DB00454MeperidineGlutamate receptor ionotropic, NMDA 2Ctarget
DB00454MeperidineGlutamate receptor ionotropic, NMDA 2Dtarget
DB00454MeperidineCytochrome P450 2C19enzyme
DB00454MeperidineCytochrome P450 3A4enzyme
DB00454MeperidineSerum albumincarrier
DB00454MeperidineAlpha-1-acid glycoprotein 1carrier
DB00454MeperidineMuscarinic acetylcholine receptortarget
DB00454MeperidineMu-type opioid receptortarget
DB00454MeperidineSodium-dependent dopamine transportertarget
DB00454MeperidineSodium-dependent noradrenaline transportertarget
DB00454MeperidineSodium-dependent serotonin transportertarget
DB00454MeperidineLiver carboxylesterase 1target
DB00454MeperidineCytochrome P450 1A2enzyme
DB00726TrimipramineSodium-dependent serotonin transportertarget
DB00726TrimipramineSodium-dependent noradrenaline transportertarget
DB00726TrimipramineCytochrome P450 2D6enzyme
DB00726TrimipramineSodium-dependent dopamine transportertarget
DB00726Trimipramine5-hydroxytryptamine receptor 2Atarget
DB00726Trimipramine5-hydroxytryptamine receptor 1Atarget
DB00726TrimipramineAlpha-1A adrenergic receptortarget
DB00726TrimipramineAlpha-1B adrenergic receptortarget
DB00726TrimipramineD(2) dopamine receptortarget
DB00726TrimipramineAlpha-2B adrenergic receptortarget
DB00726TrimipramineHistamine H1 receptortarget
DB00726TrimipramineCytochrome P450 2C19enzyme
DB00726TrimipramineCytochrome P450 3A4enzyme
DB00726TrimipramineMultidrug resistance protein 1transporter
DB00726TrimipramineCytochrome P450 2C9enzyme
DB00726Trimipramine5-hydroxytryptamine receptor 2Ctarget
DB00726Trimipramine5-hydroxytryptamine receptor 3Atarget
DB00726Trimipramine5-hydroxytryptamine receptor 1Dtarget
DB00726TrimipramineAlpha-2A adrenergic receptortarget
DB00726TrimipramineD(1) dopamine receptortarget
DB00726TrimipramineBeta adrenergic receptortarget
DB00726TrimipramineMuscarinic acetylcholine receptortarget
DB00726Trimipramine5-hydroxytryptamine receptor 1Ctarget
DB11823EsketamineNMDA receptortarget
DB11823EsketamineCytochrome P450 2B6enzyme
DB11823EsketamineCytochrome P450 3A4enzyme
DB11823EsketamineCytochrome P450 2C19enzyme
DB11823EsketamineCytochrome P450 2C9enzyme
DB11823EsketamineSodium-dependent dopamine transportertransporter
DB11823EsketamineSodium hydroxidecarrier
DB11823EsketamineEdetate disodiumcarrier
DB11823EsketamineCitric acid monohydratecarrier
DB11823EsketamineGlutamate receptor ionotropic, NMDA 2Btarget
DB11823EsketamineElongation factor 2target
DB11823EsketamineBrain-derived neurotrophic factortarget
DB11823EsketamineBDNF/NT-3 growth factors receptortarget