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Identification
Name Clomipramine
Accession Number DB01242 (APRD00253, DB07600)
Type small molecule
Groups approved
Description

Clomipramine, the 3-chloro analog of imipramine, is a dibenzazepine-derivative tricyclic antidepressant (TCA). TCAs are structurally similar to phenothiazines. They contain a tricyclic ring system with an alkyl amine substituent on the central ring. In non-depressed individuals, clomipramine does not affect mood or arousal, but may cause sedation. In depressed individuals, clomipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Tertiary amine TCAs, such as clomipramine, are more potent inhibitors of serotonin reuptake than secondary amine TCAs, such as nortriptyline and desipramine. TCAs also down-regulate cerebral cortical β-adrenergic receptors and sensitize post-synaptic serotonergic receptors with chronic use. The antidepressant effects of TCAs are thought to be due to an overall increase in serotonergic neurotransmission. TCAs also block histamine-H1 receptors, α1-adrenergic receptors and muscarinic receptors, which accounts for their sedative, hypotensive and anticholinergic effects (e.g. blurred vision, dry mouth, constipation, urinary retention), respectively. See toxicity section below for a complete listing of side effects. Clomipramine may be used to treat obsessive-compulsive disorder and disorders with an obsessive-compulsive component (e.g. depression, schizophrenia, Tourette’s disorder). Unlabeled indications include panic disorder, chronic pain (e.g. central pain, idiopathic pain disorder, tension headache, diabetic peripheral neuropathy, neuropathic pain), cataplexy and associated narcolepsy, autistic disorder, trichotillomania, onchophagia, stuttering, premature ejaculation, and premenstrual syndrome. Clomipramine is rapidly absorbed from the gastrointestinal tract and demethylated in the liver to its primary active metabolite, desmethylclomipramine.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
3-Chloroimipramine
Chlorimipramine
Clomipramina [INN-Spanish]
Clomipramine HCL
Clomipraminum [INN-Latin]
Monochlorimipramine
Salts Not Available
Brand names
Name Company
Anafranil Mallinckrodt
Hydiphen
Brand mixtures Not Available
Categories
  • Antidepressive Agents, Tricyclic
  • Serotonin Uptake Inhibitors
CAS number 303-49-1
Weight Average: 314.852
Monoisotopic: 314.154976453
Chemical Formula C19H23ClN2
InChI Key InChIKey=GDLIGKIOYRNHDA-UHFFFAOYSA-N
InChI
InChI=1S/C19H23ClN2/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3
Plain Text
IUPAC Name
(3-{5-chloro-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaen-2-yl}propyl)dimethylamine
SMILES
CN(C)CCCN1C2=CC=CC=C2CCC2=C1C=C(Cl)C=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Dibenzazepines and Derivatives
Substructures
  • Dibenzazepines and Derivatives
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Anilines
Pharmacology
Indication May 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.
Pharmacodynamics Clomipramine, a tricyclic antidepressant, is the 3-chloro derivative of Imipramine. It was thought that tricyclic antidepressants work exclusively by inhibiting the re-uptake of the neurotransmitters norepinephrine and serotonin by nerve cells. However, this response occurs immediately, yet mood does not lift for around two weeks. It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: α1 and β1 receptors are sensitized, α2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain.
Mechanism of action Clomipramine is a strong, but not completely selective serotonin reuptake inhibitor (SRI), as the active main metabolite desmethyclomipramine acts preferably as an inhibitor of noradrenaline reuptake. α1-receptor blockage and β-down-regulation have been noted and most likely play a role in the short term effects of clomipramine. A blockade of sodium-channels and NDMA-receptors might, as with other tricyclics, account for its effect in chronic pain, in particular the neuropathic type.
Absorption Well absorbed from the GI tract following oral administration. Bioavailability is approximately 50% orally due to extensive first-pass metabolism. Bioavailability is not affected by food. Peak plasma concentrations occur 2-6 hours following oral administration of a single 50 mg dose. Large interindividual variations in plasma concentrations occur, partly due to genetic differences in clomipramine metabolism. On average, steady state plasma concentrations are achieved in 1-2 weeks following multiple dose oral administration. Smoking appears to lower the steady-state plasma concentration of clomipramine, but not its active metabolite desmethylclomipramine.
Volume of distribution

Average ~ 17 L/kg (range: 9-25 L/kg)
Protein binding Clomipramine is approximately 97-98% bound to plasma proteins, principally to albumin and possibly to α1-acid glycoprotein. Desmethylclomipramine is 97-99% bound to plasma proteins.
Metabolism Extensively metabolized in the liver. The main active metabolite is desmethylclomipramine, which is formed by N-demethylation of clomipramine via CYP2C19, 3A4 and 1A2. Other metabolites and their glucuronide conjugates are also produced. Other metabolites of clomipramine include 8-hydroxyclomipramine formed via 8-hydroxylation, 2-hydroxyclomipramine formed via 2-hydroxylation, and clomipramine N-oxide formed by N-oxidation. Desmethylclomipramine is further metabolized to 8-hydroxydesmethylclomipramine and didesmethylclomipramine, which are formed by 8-hydroxylation and N-demethylation, respectively. 8-Hydroxyclomipramine and 8-hydroxydesmethylclomipramine are pharmacologically active; however, their clinical contribution remains unknown.
Route of elimination Urine (51-60%) and feces via biliary elimination (24-32%)
Half life Following oral administration of a single 150 mg dose of clomipramine, the average elimination half-life of clomipramine was 32 hours (range: 19-37 hours) and of desmethylclomipramine was 69 hours (range: 54-77 hours). Elimination half-life may vary substantially with different doses due to probably saturable kinetics (i.e. metabolism).
Clearance Not Available
Toxicity Signs and symptoms vary in severity depending upon factors such as the amount of drug absorbed, the age of the patient, and the time elapsed since drug ingestion. Critical manifestations of overdose include cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic toxicity. In U.S. clinical trials, 2 deaths occurred in 12 reported cases of acute overdosage with Anafranil either alone or in combination with other drugs. One death involved a patient suspected of ingesting a dose of 7000 mg. The second death involved a patient suspected of ingesting a dose of 5750 mg. Side effects include: sedation, hypotension, blurred vision, dry mouth, constipation, urinary retention, postural hypotension, tachycardia, hypertension, ECG changes, heart failure, impaired memory and delirium, and precipitation of hypomanic or manic episodes in bipolar depression. Withdrawal symptoms include gastrointestinal disturbances, anxiety, and insomnia.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Tyco healthcare group lp
  • Mylan pharmaceuticals inc
  • Sandoz inc
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Capsule Oral 25 mg
Capsule Oral 50 mg
Capsule Oral 75 mg
Prices
Unit description Cost Unit
Clomipramine hcl powder 17.88 USD g
Anafranil 25 mg capsule 13.51 USD capsule
Anafranil 50 mg capsule 13.51 USD capsule
Anafranil 75 mg capsule 13.24 USD capsule
ClomiPRAMINE HCl 75 mg capsule 1.55 USD capsule
Clomipramine 75 mg capsule 1.33 USD capsule
Clomipramine 50 mg capsule 1.01 USD capsule
ClomiPRAMINE HCl 25 mg capsule 0.88 USD capsule
Anafranil 50 mg Tablet 0.77 USD tablet
Clomipramine 25 mg capsule 0.75 USD capsule
ClomiPRAMINE HCl 50 mg capsule 0.57 USD capsule
Apo-Clomipramine 50 mg Tablet 0.43 USD tablet
Co Clomipramine 50 mg Tablet 0.43 USD tablet
Anafranil 25 mg Tablet 0.42 USD tablet
Anafranil 10 mg Tablet 0.31 USD tablet
Apo-Clomipramine 25 mg Tablet 0.23 USD tablet
Co Clomipramine 25 mg Tablet 0.23 USD tablet
Apo-Clomipramine 10 mg Tablet 0.17 USD tablet
Co Clomipramine 10 mg Tablet 0.17 USD tablet
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Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 189.5 °C PhysProp
boiling point 160-170 °C at 3.00E-01 mm Hg PhysProp
water solubility 0.294 mg/L Not Available
logP 5.19 HANSCH,C ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 1.44e-02 g/l ALOGPS
logP 5.04 ALOGPS
logP 4.88 ChemAxon
logS -4.3 ALOGPS
pKa (strongest basic) 9.2 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 2 ChemAxon
hydrogen donor count 0 ChemAxon
polar surface area 6.48 ChemAxon
rotatable bond count 4 ChemAxon
refractivity 95.41 ChemAxon
polarizability 35.73 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Compound C06918 Link_out
PubChem Compound 2801 Link_out
PubChem Substance 46505157 Link_out
ChemSpider 2699 Link_out
BindingDB 50021927 Link_out
ChEBI 47780 Link_out
ChEMBL 47780 Link_out
Therapeutic Targets Database DAP000742 Link_out
PharmGKB PA449048 Link_out
IUPHAR 2398 Link_out
Guide to Pharmacology 2398 Link_out
HET CXX Link_out
Drug Product Database 2244818 Link_out
RxList http://www.rxlist.com/cgi/generic/clomipr.htm Link_out
Drugs.com http://www.drugs.com/cdi/clomipramine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/ana1020.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Clomipramine Link_out
ATC Codes
  • N06AA04
AHFS Codes
  • 28:16.04.28
PDB Entries Not Available
FDA label show (712 KB)
MSDS show (74.2 KB)
Interactions
Drug Interactions
Drug Interaction
Altretamine Risk of severe hypotension
Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Atazanavir Atazanavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if atazanavir is initiated, discontinued or dose changed.
Butabarbital Barbiturates like butabarbital may increase the metabolism of tricyclic antidepressants like clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Butalbital Barbiturates such as butalbital may increase the metabolism of tricyclic antidepressants such as clomipramine. Monitor for decreased therapeutic effects of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. The tricyclic antidepressant dosage will likely need to be increased during concomitant barbiturate therapy, and reduced upon barbiturate discontinuation.
Cimetidine Cimetidine may increase the effect of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if cimetidine is initiated, discontinued or dose changed.
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonidine The tricyclic antidepressant, clomipramine, may decrease the effect of clonidine.
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Dihydroquinidine barbiturate Dihydroquinidine barbiturate increases the effect of the tricyclic antidepressant, clomipramine.
Dobutamine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of dobutamine.
Donepezil Possible antagonism of action
Dopamine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of dopamine.
Ephedra The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedra.
Ephedrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of ephedrine.
Epinephrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of epinephrine.
Fenoterol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of fenoterol.
Fluoxetine The SSRI, fluoxetine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluoxetine is initiated, discontinued or dose changed.
Fluvoxamine The SSRI, fluvoxamine, may increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Additive modulation of serotonin activity also increases the risk of serotonin syndrome. Monitor for development of serotonin syndrome during concomitant therapy. Monitor for changes in the therapeutic and adverse effects of clomipramine if fluvoxamine is initiated, discontinued or dose changed.
Galantamine Possible antagonism of action
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine The tricyclic antidepressant, clomipramine, decreases the effect of guanethidine.
Isocarboxazid Possibility of severe adverse effects
Isoproterenol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of isoproterenol.
Mephentermine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of mephentermine.
Metaraminol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of metaraminol.
Methoxamine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of methoxamine.
Moclobemide Possible severe adverse reaction with this combination
Norepinephrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of norepinephrine.
Orciprenaline The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of orciprenaline.
Phenelzine Possibility of severe adverse effects
Phenylephrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylephrine.
Phenylpropanolamine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of phenylpropanolamine.
Pirbuterol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pirbuterol.
Procaterol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of procaterol.
Pseudoephedrine The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of pseudoephedrine.
Quinidine Additive QTc-prolonging effects may occur. Quinidine may also increase the serum concentration of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if quinidine is initiated, discontinued or dose changed. Monitor for the development of torsades de pointes during concomitant therapy.
Quinidine barbiturate Quinidine barbiturate increases the effect of tricyclic antidepressant, clomipramine.
Rasagiline Possibility of severe adverse effects
Rifabutin The rifamycin, rifabutin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifabutin is initiated, discontinued or dose changed.
Rifampin The rifamycin, rifampin, may decrease the effect of the tricyclic antidepressant, clomipramine, by increasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if rifampin is initiated, discontinued or dose changed.
Ritonavir Ritonavir may increase the effect and toxicity of the tricyclic antidepressant, clomipramine, by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of clomipramine if ritonavir if initiated, discontinued or dose changed.
Rivastigmine Possible antagonism of action
Salbutamol The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of salbutamol.
Sibutramine Increased risk of CNS adverse effects
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Tacrine The therapeutic effects of the central acetylcholinesterase inhibitor, Tacrine, and/or the anticholinergic, Clomipramine, may be reduced due to antagonism. The interaction may be beneficial when the anticholinergic action is a side effect. Monitor for decreased efficacy of both agents.
Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Tamoxifen Clomipramine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
Tamsulosin Clomipramine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Clomipramine is initiated, discontinued, or dose changed.
Terbinafine Terbinafine may reduce the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for therapeutic/adverse effects of Clomipramine if Terbinafine is initiated, discontinued or dose changed.
Terbutaline The tricyclic antidepressant, clomipramine, increases the sympathomimetic effect of terbutaline.
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Clomipramine by decreasing Clomipramine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Clomipramine if Thiabendazole is initiated, discontinued or dose changed.
Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
Ticlopidine Ticlopidine may decrease the metabolism and clearance of Clomipramine. Consider alternate therapy or monitor for adverse/toxic effects of Clomipramine if Ticlopidine is initiated, discontinued or dose changed.
Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
Tramadol Tramadol increases the risk of serotonin syndrome and seizures. Clomipramine may decrease the effect of Tramadol by decreasing active metabolite production.
Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimethobenzamide Trimethobenzamide and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome. Additive QTc-prolongation may also occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
Triprolidine Triprolidine and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhance their adverse/toxic effects. Additive CNS depressant effects may also occur. Monitor for enhanced anticholinergic and CNS depressant effects.
Trospium Trospium and Clomipramine, two anticholinergics, may cause additive anticholinergic effects and enhanced adverse/toxic effects. Monitor for enhanced anticholinergic effects.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and clomipramine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Food Interactions
  • Avoid alcohol.
  • Grapefruit and grapefruit juice should be avoided throughout treatment, grapefruit can modify serum levels of clomipramine and its metabolite desmethyl-clomipramine.
  • Take with food to reduce irritation.
Targets

1. Sodium-dependent serotonin transporter

Pharmacological action: yes
Actions: inhibitor

Terminates the action of serotonine by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P31645 Link_out
Gene: SLC6A4 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Alvarez JC, Gluck N, Arnulf I, Quintin P, Leboyer M, Pecquery R, Launay JM, Perez-Diaz F, Spreux-Varoquaux O: Decreased platelet serotonin transporter sites and increased platelet inositol triphosphate levels in patients with unipolar depression: effects of clomipramine and fluoxetine. Clin Pharmacol Ther. 1999 Dec;66(6):617-24. Pubmed
  2. Borkowska A, Pilaczynska E, Araszkiewicz A, Rybakowski J: [The effect of sertraline on cognitive functions in patients with obsessive-compulsive disorder] Psychiatr Pol. 2002 Nov-Dec;36(6 Suppl):289-95. Pubmed
  3. Suhara T, Takano A, Sudo Y, Ichimiya T, Inoue M, Yasuno F, Ikoma Y, Okubo Y: High levels of serotonin transporter occupancy with low-dose clomipramine in comparative occupancy study with fluvoxamine using positron emission tomography. Arch Gen Psychiatry. 2003 Apr;60(4):386-91. Pubmed
  4. Larsen AK, Brennum LT, Egebjerg J, Sanchez C, Halldin C, Andersen PH: Selectivity of (3)H-MADAM binding to 5-hydroxytryptamine transporters in vitro and in vivo in mice; correlation with behavioural effects. Br J Pharmacol. 2004 Mar;141(6):1015-23. Epub 2004 Mar 1. Pubmed
  5. Malizia AL, Melichar JM, Brown DJ, Gunn RN, Reynolds A, Jones T, Nutt DJ: Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo. J Psychopharmacol. 1997;11(3):279-81. Pubmed
  6. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
  7. Gillman PK: Tricyclic antidepressant pharmacology and therapeutic drug interactions updated. Br J Pharmacol. 2007 Jul;151(6):737-48. Epub 2007 Apr 30. Pubmed

2. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Hentall ID, Kurle PJ, White TR: Correlations between serotonin level and single-cell firing in the rat’s nucleus raphe magnus. Neuroscience. 2000;95(4):1081-8. Pubmed
  2. Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. Pubmed
  3. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. Pubmed
  4. Trifunovic RD, Brodie MS: The effects of clomipramine on the excitatory action of ethanol on dopaminergic neurons of the ventral tegmental area in vitro. J Pharmacol Exp Ther. 1996 Jan;276(1):34-40. Pubmed
  5. Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. Pubmed

3. 5-hydroxytryptamine 2B receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P41595 Link_out
Gene: HTR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. Pubmed
  2. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. Pubmed
  3. Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. Pubmed

4. 5-hydroxytryptamine 2C receptor

Pharmacological action: yes
Actions: antagonist

This is one of the several different receptors for 5- hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Sargent PA, Quested DJ, Cowen PJ: Clomipramine enhances the cortisol response to 5-HTP: implications for the therapeutic role of 5-HT2 receptors. Psychopharmacology (Berl). 1998 Nov;140(1):120-2. Pubmed
  2. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. Pubmed
  3. Contreras CM, Marvan ML, Munoz-Mendez A, Ramirez-Morales A: Cortical and septal responses to dorsal raphe nucleus stimulation in the rat: long-term clomipramine actions. Bol Estud Med Biol. 1992 Jan-Dec;40(1-4):3-7. Pubmed

5. Sodium-dependent noradrenaline transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out
Gene: SLC6A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. Pubmed
  2. Jungkun G, Kuss HJ, Gsell W: Long-term effects of tricyclic antidepressants on norepinephrine kinetics in humans. J Neural Transm. 2001;108(3):349-62. Pubmed

6. Glutathione S-transferase P

Pharmacological action: unknown
Actions: inhibitor

Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles

Organism class: human
UniProt ID: P09211 Link_out
Gene: GSTP1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Baranczyk-Kuzma A, Sawicki J, Kuzma M, Jagiello J: [Tricyclic antidepressants as inhibitors of brain glutathione-S-transferase] Pol Merkur Lekarski. 2001 Dec;11(66):472-5. Pubmed
  2. Baranczyk-Kuzma A, Kuzma M, Gutowicz M, Kazmierczak B, Sawicki J: Glutathione S-transferase pi as a target for tricyclic antidepressants in human brain. Acta Biochim Pol. 2004;51(1):207-12. Pubmed
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

7. Transporter

Pharmacological action: unknown
Organism class: bacterial
UniProt ID: O67854 Link_out
Gene: snf Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed
Enzymes

1. Cytochrome P450 2D6

Actions: substrate, inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C19

Actions: substrate

Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine

UniProt ID: P33261 Link_out
Gene: CYP2C19 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Application available online: The P450 Program
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out
Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. http://www.mentalhealth.com/drug/p30-a01.html Source
  3. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Application available online: The P450 Program
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mahar Doan KM, Humphreys JE, Webster LO, Wring SA, Shampine LJ, Serabjit-Singh CJ, Adkison KK, Polli JW: Passive permeability and P-glycoprotein-mediated efflux differentiate central nervous system (CNS) and non-CNS marketed drugs. J Pharmacol Exp Ther. 2002 Dec;303(3):1029-37. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:20