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Showing toxin card for Amitriptyline (T3D2480)

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Version 1.0
Creation Date 2009-07-03 22:04:59
Update Date 2010-05-18 20:57:20
Accession Number T3D2480
Name Amitriptyline
Compound Type
  • Adrenergic Uptake Inhibitor
  • Analgesic, Non-Narcotic
  • Antidepressive Agent, Tricyclic
  • Drug
Description Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antagonize cholinergic and alpha-1 adrenergic responses to bioactive amines. [PubChem]
Synonyms
  1. Amitriprolidine
  2. Amitriptylin
  3. Amitriptyline HCL
  4. Amitriptyline Hydrochloride
  5. Amitryptiline
  6. Amitryptyline
  7. Amytriptiline
Chemical IUPAC Name dimethyl(3-{tricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3,5,7,11,13-hexaen-2-ylidene}propyl)amine
Chemical Formula C20H23N
Chemical Structure Structure
CAS Registry Number 50-48-6
InChI Identifier InChI=1S/C20H23N/c1-21(2)15-7-12-20-18-10-5-3-8-16(18)13-14-17-9-4-6-11-19(17)20/h3-6,8-12H,7,13-15H2,1-2H3
InChI Key InChIKey=KRMDCWKBEZIMAB-UHFFFAOYSA-N
PubChem Compound ID 2160 Link Image
KEGG ID C06824 Link Image
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 2666 Link Image
BioCyc ID Not Available
SuperToxic ID Not Available
CTD ID D000639 Link Image
Stitch ID Amitriptyline Link Image
DrugBank ID DB00321 Link Image
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Amitriptyline Link Image
Monoisotopic Mass 277.18305
MOL File Show
PDB File Show
SDF File Show
SMILES CN(C)CCC=C1C2=CC=CC=C2CCC2=CC=CC=C12
Appearance White, odorless, crystalline compound (S438).
Melting Point 196-197 oC
Solubility 9.7 mg/mL
Predicted LogP 4.8095
Route of Exposure oral (S405)
Mechanism of Action Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Metabolism Amitriptyline is rapidly and well absorbed following oral administrationExclusively hepatic, with first pass effect. It is demethylated in the liver to its primary active metabolite, nortriptyline (S405).
Toxicity Values LD50: 350 mg/kg (Oral, Mouse) (S405)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources It is used as an antidepressant drug (S405).
Minimum Risk Level Not Available
Health Effects Some rare side effects include tinnitus, hypotension, mania, psychosis, heart block, arrhythmias, lip and mouth ulcers, extrapyramidal symptoms, depression, and hepatic toxicity.Amitriptyline exhibits strong anticholinergic activity, cardiovascular effects including orthostatic hypotension, changes in heart rhythm and conduction, and a lowering of the seizure threshold (S405, S438).
Symptoms Symptoms of overdose include abnormally low blood pressure, confusion, convulsions, dilated pupils and other eye problems, disturbed concentration, drowsiness, hallucinations, impaired heart function, rapid or irregular heartbeat, reduced body temperature, stupor, and unresponsiveness or coma.
Treatment Consider gastric lavage only if within one hour of a potentially fatal overdose. Give 50 grams of charcoal if within one hour of ingestion. Prolonged resuscitation may be successful in case of cardiac arrest. Give sodium bicarbonate in case of arrhythmias. (S440)
General References
  • T558 - Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, Komatsu K, Ohba R, Oyake J, Hatakeyama N, Watanabe S: New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005 Jun;21 Suppl 2:42-6. [PubMed Link Image]
  • T557 - Drugs.com
  • S405 - DrugBank: a knowledgebase for drugs, drug actions and drug targets. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. [PubMed Link Image]
  • S440 - Kerr GW, McGuffie AC, and Wilkie S. Tricyclic antidepressant overdose: a review. Emerg. Med. J. 2001;18;236-241. [PubMed Link Image]
  • S438 - Wikipedia. Amitriptyline. Last Updated 7 August 2009.
Targets
  1. Sodium-dependent serotonin transporter
  2. Sodium-dependent noradrenaline transporter
  3. Potassium voltage-gated channel subfamily KQT member 2
  4. Alpha-2A adrenergic receptor
Target 1 [top]
Target 1 ID 1141
Target 1 Name Sodium-dependent serotonin transporter
Target 1 Mechanism of Action Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Target 1 Description Terminates the action of serotonin by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 1 Synonyms
  1. 5HT transporter; 5HTT; Solute carrier family 6 member 4
Target 1 Gene Name SLC6A4
Target 1 Protein Sequence >Sodium-dependent serotonin transporter 
METTPLNSQKQLSACEDGEDCQENGVLQKVVPTPGDKVESGQISNGYSAVPSPGAGDDTR
HSIPATTTTLVAELHQGERETWGKKVDFLLSVIGYAVDLGNVWRFPYICYQNGGGAFLLP
YTIMAIFGGIPLFYMELALGQYHRNGCISIWRKICPIFKGIGYAICIIAFYIASYYNTIM
AWALYYLISSFTDQLPWTSCKNSWNTGNCTNYFSEDNITWTLHSTSPAEEFYTRHVLQIH
RSKGLQDLGGISWQLALCIMLIFTVIYFSIWKGVKTSGKVVWVTATFPYIILSVLLVRGA
TLPGAWRGVLFYLKPNWQKLLETGVWIDAAAQIFFSLGPGFGVLLAFASYNKFNNNCYQD
ALVTSVVNCMTSFVSGFVIFTVLGYMAEMRNEDVSEVAKDAGPSLLFITYAEAIANMPAS
TFFAIIFFLMLITLGLDSTFAGLEGVITAVLDEFPHVWAKRRERFVLAVVITCFFGSLVT
LTFGGAYVVKLLEEYATGPAVLTVALIEAVAVSWFYGITQFCRDVKEMLGFSPGWFWRIC
WVAISPLFLLFIICSFLMSPPQLRLFQYNYPYWSIILGYCIGTSSFICIPTYIAYRLIIT
PGTFKERIIKSITPETPTEIPCGDIRLNAV
Target 1 Number of Residues 630
Target 1 Molecular Weight 70324.2
Target 1 Theoretical pI 6.17
Target 1 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 1 General Function Involved in protein binding
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 88-108
  • 116-135
  • 160-180
  • 253-271
  • 280-297
  • 333-350
  • 362-383
  • 417-436
  • 464-482
  • 498-518
  • 539-558
  • 577-595
Target 1 Essentiality Non Essential
Target 1 Domain Function PF03491:5HT_transporter PF00209:SNF
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB ID P31645 Link Image
Target 1 Cellular Location Membrane
Target 1 Gene Sequence >1893 bp 
ATGGAGACGACGCCCTTGAATTCTCAGAAGCAGCTATCAGCGTGTGAAGATGGAGAAGAT
TGTCAGGAAAACGGAGTTCTACAGAAGGTTGTTCCCACCCCAGGGGACAAAGTGGAGTCC
GGGCAAATATCCAATGGGTACTCAGCAGTTCCAAGTCCTGGTGCGGGAGATGACACACGG
CACTCTATCCCAGCGACCACCACCACCCTAGTGGCTGAGCTTCATCAAGGGGAACGGGAG
ACCTGGGGCAAGAAGGTGGATTTCCTTCTCTCAGTGATTGGCTATGCTGTGGACCTGGGC
AATGTCTGGCGCTTCCCCTACATATGTTACCAGAATGGAGGGGGGGCATTCCTCCTCCCC
TACACCATCATGGCCATTTTTGGGGGAATCCCGCTCTTTTACATGGAGCTCGCACTGGGA
CAGTACCACCGAAATGGATGCATTTCAATATGGAGGAAAATCTGCCCGATTTTCAAAGGG
ATTGGTTATGCCATCTGCATCATTGCCTTTTACATTGCTTCCTACTACAACACCATCATG
GCCTGGGCGCTATACTACCTCATCTCCTCCTTCACGGACCAGCTGCCCTGGACCAGCTGC
AAGAACTCCTGGAACACTGGCAACTGCACCAATTACTTCTCCGAGGACAACATCACCTGG
ACCCTCCATTCCACGTCCCCTGCTGAAGAATTTTACACGCGCCACGTCCTGCAGATCCAC
CGGTCTAAGGGGCTCCAGGACCTGGGGGGCATCAGCTGGCAGCTGGCCCTCTGCATCATG
CTGATCTTCACTGTTATCTACTTCAGCATCTGGAAAGGCGTCAAGACCTCTGGCAAGGTG
GTGTGGGTGACAGCCACCTTCCCTTATATCATCCTTTCTGTCCTGCTGGTGAGGGGTGCC
ACCCTCCCTGGAGCCTGGAGGGGTGTTCTCTTCTACTTGAAACCCAATTGGCAGAAACTC
CTGGAGACAGGGGTGTGGATAGATGCAGCCGCTCAGATCTTCTTCTCTCTTGGTCCGGGC
TTTGGGGTCCTGCTGGCTTTTGCTAGCTACAACAAGTTCAACAACAACTGCTACCAAGAT
GCCCTGGTGACCAGCGTGGTGAACTGCATGACGAGCTTCGTTTCGGGATTTGTCATCTTC
ACAGTGCTCGGTTACATGGCTGAGATGAGGAATGAAGATGTGTCTGAGGTGGCCAAAGAC
GCAGGTCCCAGCCTCCTCTTCATCACGTATGCAGAAGCGATAGCCAACATGCCAGCGTCC
ACTTTCTTTGCCATCATCTTCTTTCTGATGTTAATCACGCTGGGCTTGGACAGCACGTTT
GCAGGCTTGGAGGGGGTGATCACGGCTGTGCTGGATGAGTTCCCACACGTCTGGGCCAAG
CGCCGGGAGCGGTTCGTGCTCGCCGTGGTCATCACCTGCTTCTTTGGATCCCTGGTCACC
CTGACTTTTGGAGGGGCCTACGTGGTGAAGCTGCTGGAGGAGTATGCCACGGGGCCCGCA
GTGCTCACTGTCGCGCTGATCGAAGCAGTCGCTGTGTCTTGGTTCTATGGCATCACTCAG
TTCTGCAGGGACGTGAAGGAAATGCTCGGCTTCAGCCCGGGGTGGTTCTGGAGGATCTGC
TGGGTGGCCATCAGCCCTCTGTTTCTCCTGTTCATCATTTGCAGTTTTCTGATGAGCCCG
CCACAACTACGACTTTTCCAATATAATTATCCTTACTGGAGTATCATCTTGGGTTACTGC
ATAGGAACCTCATCTTTCATTTGCATCCCCACATATATAGCTTATCGGTTGATCATCACT
CCAGGGACATTTAAAGAGCGTATTATTAAAAGTATTACCCCGGAGACACCAACAGAAATT
CCTTGTGGGGACATCCGCTTGAATGCTGTGTAA
Target 1 GenBank Gene ID Not Available
Target 1 GeneCard ID SLC6A4 Link Image
Target 1 GenAtlas ID SLC6A4 Link Image
Target 1 HGNC ID HGNC:11050 Link Image
Target 1 Chromosome Location Chromosome:17
Target 1 Locus 17q11.1-q12
Target 1 SNPs SNPJam Report Link Image
Target 1 Toxin References
  • T562 - Ushijima K, Sakaguchi H, Sato Y, To H, Koyanagi S, Higuchi S, Ohdo S: Chronopharmacological study of antidepressants in forced swimming test of mice. J Pharmacol Exp Ther. 2005 Nov;315(2):764-70. Epub 2005 Aug 3. [PubMed Link Image]
  • T561 - Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29. [PubMed Link Image]
  • T563 - Kalia M: Neurobiological basis of depression: an update. Metabolism. 2005 May;54(5 Suppl 1):24-7. [PubMed Link Image]
  • T453 - Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [PubMed Link Image]
  • T462 - Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [PubMed Link Image]
Target 1 General References 8452685; 7681602; 7684072; 15489334; 16803896; 10391209; 14593431; 12869649
Target 2 [top]
Target 2 ID 1152
Target 2 Name Sodium-dependent noradrenaline transporter
Target 2 Mechanism of Action Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Target 2 Description Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals
Target 2 Synonyms
  1. Norepinephrine transporter; NET; Solute carrier family 6 member 2
Target 2 Gene Name SLC6A2
Target 2 Protein Sequence >Sodium-dependent noradrenaline transporter 
MLLARMNPQVQPENNGADTGPEQPLRARKTAELLVVKERNGVQCLLAPRDGDAQPRETWG
KKIDFLLSVVGFAVDLANVWRFPYLCYKNGGGAFLIPYTLFLIIAGMPLFYMELALGQYN
REGAATVWKICPFFKGVGYAVILIALYVGFYYNVIIAWSLYYLFSSFTLNLPWTDCGHTW
NSPNCTDPKLLNGSVLGNHTKYSKYKFTPAAEFYERGVLHLHESSGIHDIGLPQWQLLLC
LMVVVIVLYFSLWKGVKTSGKVVWITATLPYFVLFVLLVHGVTLPGASNGINAYLHIDFY
RLKEATVWIDAATQIFFSLGAGFGVLIAFASYNKFDNNCYRDALLTSSINCITSFVSGFA
IFSILGYMAHEHKVNIEDVATEGAGLVFILYPEAISTLSGSTFWAVVFFVMLLALGLDSS
MGGMEAVITGLADDFQVLKRHRKLFTFGVTFSTFLLALFCITKGGIYVLTLLDTFAAGTS
ILFAVLMEAIGVSWFYGVDRFSNDIQQMMGFRPGLYWRLCWKFVSPAFLLFVVVVSIINF
KPLTYDDYIFPPWANWVGWGIALSSMVLVPIYVIYKFLSTQGSLWERLAYGITPENEHHL
VAQRDIRQFQLQHWLAI
Target 2 Number of Residues 617
Target 2 Molecular Weight 69331.4
Target 2 Theoretical pI 7.53
Target 2 GO Classification
Function
transporter activity
neurotransmitter transporter activity
neurotransmitter:sodium symporter activity
Process
physiological process
cellular physiological process
transport
neurotransmitter transport
Component
cell
membrane
intrinsic to membrane
integral to membrane
integral to plasma membrane
Target 2 General Function Involved in norephinephrine:sodium symporter activity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 65-85
  • 93-112
  • 136-156
  • 235-253
  • 262-279
  • 315-332
  • 344-365
  • 398-417
  • 444-462
  • 478-498
  • 519-538
  • 557-575
Target 2 Essentiality Non Essential
Target 2 Domain Function PF00209:SNF
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB ID P23975 Link Image
Target 2 Cellular Location Membrane
Target 2 Gene Sequence >1854 bp 
ATGCTTCTGGCGCGGATGAACCCGCAGGTGCAGCCCGAGAACAACGGGGCGGACACGGGT
CCAGAGCAGCCCCTTCGGGCGCGCAAAACTGCGGAGCTGCTGGTGGTGAAGGAGCGCAAC
GGCGTCCAGTGCCTGCTGGCGCCCCGCGACGGCGACGCGCAGCCCCGGGAGACCTGGGGC
AAGAAGATCGACTTCCTGCTGTCCGTAGTCGGCTTCGCAGTGGACCTGGCCAACGTGTGG
CGCTTCCCCTACCTCTGCTACAAGAACGGCGGCGGTGCCTTCTTGATCCCGTACACACTG
TTCCTTATCATCGCGGGGATGCCCCTGTTCTACATGGAGCTGGCTCTGGGACAGTACAAC
CGGGAGGGGGCTGCCACCGTTTGGAAAATCTGCCCATTCTTCAAAGGCGTTGGCTATGCT
GTCATCCTGATCGCCCTGTACGTTGGCTTCTACTACAACGTCATCATCGCCTGGTCACTC
TACTACCTCTTCTCCTCCTTCACCCTCAACCTGCCCTGGACCGACTGTGGCCACACCTGG
AACAGCCCCAACTGTACCGACCCCAAGCTCCTCAATGGCTCCGTGCTTGGCAACCACACC
AAGTACTCCAAGTACAAGTTCACGCCGGCAGCCGAGTTTTATGAGCGTGGTGTCCTGCAC
CTTCACGAGAGCAGCGGGATTCATGACATCGGCCTGCCCCAGTGGCAGCTCTTGCTCTGT
CTGATGGTCGTCGTCATCGTCTTGTATTTTAGCCTCTGGAAAGGGGTGAAGACATCAGGA
AAGGTGGTGTGGATCACAGCCACGCTGCCTTACTTCGTGCTGTTCGTGCTCCTGGTCCAT
GGCGTCACGCTGCCCGGAGCCTCCAATGGCATCAATGCCTACCTGCACATCGACTTCTAC
CGCTTGAAAGAGGCCACGGTATGGATTGATGCCGCAACTCAGATATTTTTTTCCTTGGGG
GCTGGATTTGGAGTATTGATTGCATTTGCCAGTTACAACAAATTTGACAACAACTGTTAC
AGGGATGCCCTGCTGACCAGCAGCATCAACTGTATCACCAGCTTCGTCTCTGGGTTCGCC
ATCTTCTCCATCCTTGGTTACATGGCCCATGAACACAAGGTCAACATTGAGGATGTGGCC
ACAGAAGGAGCTGGCCTAGTGTTCATCCTGTATCCAGAGGCCATTTCTACCCTGTCTGGA
TCTACATTCTGGGCTGTTGTGTTTTTCGTCATGCTCCTGGCGCTGGGCCTTGACAGCTCA
ATGGGAGGCATGGAGGCTGTCATCACGGGCCTGGCAGATGACTTCCAGGTCCTGAAGCGA
CACCGGAAACTCTTCACATTTGGCGTCACCTTCAGCACTTTCCTTCTCGCCCTGTTCTGC
ATAACCAAGGGTGGAATTTACGTCTTGACCCTCCTGGACACCTTTGCTGCGGGCACCTCC
ATCCTTTTTGCTGTCCTCATGGAAGCCATCGGAGTTTCCTGGTTTTATGGAGTGGACAGG
TTCAGCAACGACATCCAGCAGATGATGGGGTTCAGGCCGGGTCTATACTGGAGACTGTGC
TGGAAGTTCGTCAGTCCTGCCTTCCTCCTGTTCGTGGTTGTGGTCAGCATCATCAACTTC
AAGCCACTCACCTACGACGACTACATCTTCCCGCCCTGGGCCAACTGGGTGGGGTGGGGC
ATCGCCCTGTCCTCCATGGTCCTGGTGCCCATCTACGTCATCTATAAGTTCCTCAGCACG
CAGGGCTCTCTTTGGGAGAGACTGGCCTATGGCATCACGCCAGAGAACGAGCACCACCTG
GTGGCTCAGAGGGACATCAGACAGTTCCAGTTGCAACACTGGCTGGCCATCTGA
Target 2 GenBank Gene ID Not Available
Target 2 GeneCard ID SLC6A2 Link Image
Target 2 GenAtlas ID SLC6A2 Link Image
Target 2 HGNC ID HGNC:11048 Link Image
Target 2 Chromosome Location Chromosome:16
Target 2 Locus 16q12.2
Target 2 SNPs SNPJam Report Link Image
Target 2 Toxin References
  • T453 - Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [PubMed Link Image]
Target 2 General References 2008212; 7488042; 11343649; 10684912
Target 3 [top]
Target 3 ID 592
Target 3 Name Potassium voltage-gated channel subfamily KQT member 2
Target 3 Mechanism of Action Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Target 3 Description Probably important in the regulation of neuronal excitability. Associates with KCNQ3 to form a potassium channel with essentially identical properties to the channel underlying the native M-current, a slowly activating and deactivating potassium conductance which plays a critical role in determining the subthreshold electrical excitability of neurons as well as the responsiveness to synaptic inputs. KCNQ2/KCNQ3 current is blocked by linopirdine and XE991, and activated by the anticonvulsant retigabine. Muscarinic agonist oxotremorine-M strongly suppress KCNQ2/KCNQ3 current in cells in which cloned KCNQ2/KCNQ3 channels were coexpressed with M1 muscarinic receptors
Target 3 Synonyms
  1. Voltage-gated potassium channel subunit Kv7.2; Neuroblastoma-specific potassium channel subunit alpha KvLQT2; KQT-like 2
Target 3 Gene Name KCNQ2
Target 3 Protein Sequence >Potassium voltage-gated channel subfamily KQT member 2 
MVQKSRNGGVYPGPSGEKKLKVGFVGLDPGAPDSTRDGALLIAGSEAPKRGSILSKPRAG
GAGAGKPPKRNAFYRKLQNFLYNVLERPRGWAFIYHAYVFLLVFSCLVLSVFSTIKEYEK
SSEGALYILEIVTIVVFGVEYFVRIWAAGCCCRYRGWRGRLKFARKPFCVIDIMVLIASI
AVLAAGSQGNVFATSALRSLRFLQILRMIRMDRRGGTWKLLGSVVYAHSKELVTAWYIGF
LCLILASFLVYLAEKGENDHFDTYADALWWGLITLTTIGYGDKYPQTWNGRLLAATFTLI
GVSFFALPAGILGSGFALKVQEQHRQKHFEKRRNPAAGLIQSAWRFYATNLSRTDLHSTW
QYYERTVTVPMYSSQTQTYGASRLIPPLNQLELLRNLKSKSGLAFRKDPPPEPSPSKGSP
CRGPLCGCCPGRSSQKVSLKDRVFSSPRGVAAKGKGSPQAQTVRRSPSADQSLEDSPSKV
PKSWSFGDRSRARQAFRIKGAASRQNSEEASLPGEDIVDDKSCPCEFVTEDLTPGLKVSI
RAVCVMRFLVSKRKFKESLRPYDVMDVIEQYSAGHLDMLSRIKSLQSRVDQIVGRGPAIT
DKDRTKGPAEAELPEDPSMMGRLGKVEKQVLSMEKKLDFLVNIYMQRMGIPPTETEAYFG
AKEPEPAPPYHSPEDSREHVDRHGCIVKIVRSSSSTGQKNFSAPPAAPPVQCPPSTSWQP
QSHPRQGHGTSPVGDHGSLVRIPPPPAHERSLSAYGGGNRASMEFLRQEDTPGCRPPEGN
LRDSDTSISIPSVDHEELERSFSGFSISQSKENLDALNSCYAAVAPCAKVRPYIAEGESD
TDSDLCTPCGPPPRSATGEGPFGDVGWAGPRK
Target 3 Number of Residues 872
Target 3 Molecular Weight 95846.6
Target 3 Theoretical pI 9.59
Target 3 GO Classification
Function
voltage-gated ion channel activity
voltage-gated potassium channel activity
transporter activity
ion transporter activity
ion channel activity
Process
cation transport
monovalent inorganic cation transport
potassium ion transport
physiological process
cellular physiological process
transport
ion transport
Component
protein complex
voltage-gated potassium channel complex
cell
membrane
Target 3 General Function Inorganic ion transport and metabolism
Target 3 Pathways Not Available
Target 3 Reactions Not Available
Target 3 Signals
  • None
Target 3 Transmembrane Regions
  • 92-112
  • 123-143
  • 167-187
  • 196-218
  • 232-252
  • 292-312
Target 3 Essentiality Non Essential
Target 3 Domain Function PF00520:Ion_trans PF03520:KCNQ_channel
Target 3 GenBank ID Protein Not Available
Target 3 UniProtKB ID O43526 Link Image
Target 3 Cellular Location Membrane
Target 3 Gene Sequence >1182 bp 
ATGGTGCAGAAGTCGCGCAACGGCGGCGTATACCCCGGCCCGAGCGGGGAGAAGAAGCTG
AAGGTGGGCTTCGTGGGGCTGGACCCCGGCGCGCCCGACTCCACCCGGGACGGGGCGCTG
CTGATCGCCGGCTCCGAGGCCCCCAAGCGCGGCAGCATCCTCAGCAAACCTCGCGCGGGC
GGCGCGGGCGCCGGGAAGCCCCCCAAGCGCAACGCCTTCTACCGCAAGCTGCAGAATTTC
CTCTACAACGTGCTGGAGCGGCCGCGCGGCTGGGCGTTCATCTACCACGCCTACGTGTTC
CTCCTGGTTTTCTCCTGCCTCGTGCTGTCTGTGTTTTCCACCATCAAGGAGTATGAGAAG
AGCTCGGAGGGGGCCCTCTACATCCTGGAAATCGTGACTATCGTGGTGTTTGGCGTGGAG
TACTTCGTGCGGATCTGGGCCGCAGGCTGCTGCTGCCGGTACCGTGGCTGGAGGGGGCGG
CTCAAGTTTGCCCGGAAACCGTTCTGTGTGATTGACATCATGGTGCTCATCGCCTCCATT
GCGGTGCTGGCCGCCGGCTCCCAGGGCAACGTCTTTGCCACATCTGCGCTCCGGAGCCTG
CGCTTCCTGCAGATTCTGCGGATGATCCGCATGGACCGGCGGGGAGGCACCTGGAAGCTG
CTGGGCTCTGTGGTCTATGCCCACAGCAAGGAGCTGGTCACTGCCTGGTACATCGGCTTC
CTTTGTCTCATCCTGGCCTCGTTCCTGGTGTACTTGGCAGAGAAGGGGGAGAACGACCAC
TTTGACACCTACGCGGATGCACTCTGGTGGGGCCTGATCACGCTGACCACCATTGGCTAC
GGGGACAAGTACCCCCAGACCTGGAACGGCAGGCTCCTTGCGGCAACCTTCACCCTCATC
GGTGTCTCCTTCTTCGCGCTGCCTGCAGGCATCTTGGGGTCTGGGTTTGCCCTGAAGGTT
CAGGAGCAGCACAGGCAGAAGCACTTTGAGAAGAGGCGGAACCCGGCAGCAGGCCTGATC
CAGTCGGCCTGGAGATTCTACGCCACCAACCTCTCGCGCACAGACCTGCACTCCACGTGG
CAGTACTACGAGCGAACGGTCACCGTGCCCATGTACAGGTACCGCCGCCGGGCACCTGCC
ACCAAGCAACTGTTTCATTTTTTATTTTCCATTTGTTCTTAA
Target 3 GenBank Gene ID Not Available
Target 3 GeneCard ID KCNQ2 Link Image
Target 3 GenAtlas ID KCNQ2 Link Image
Target 3 HGNC ID HGNC:6296 Link Image
Target 3 Chromosome Location Chromosome:20
Target 3 Locus 20q13.3
Target 3 SNPs SNPJam Report Link Image
Target 3 Toxin References
  • T559 - Punke MA, Friederich P: Amitriptyline is a potent blocker of human Kv1.1 and Kv7.2/7.3 channels. Anesth Analg. 2007 May;104(5):1256-64, tables of contents. [PubMed Link Image]
Target 3 General References 9039501; 9425895; 9430594; 9836639; 9827540; 9677360; 11160379; 11780052; 15489334; 9872318
Target 4 [top]
Target 4 ID 1143
Target 4 Name Alpha-2A adrenergic receptor
Target 4 Mechanism of Action Amitriptyline is metabolized to nortriptyline which inhibits the reuptake of norepinephrine and serotonin almost equally. Amitriptyline inhibits the membrane pump mechanism responsible for uptake of norepinephrine and serotonin in adrenergic and serotonergic neurons. Pharmacologically this action may potentiate or prolong neuronal activity since reuptake of these biogenic amines is important physiologically in terminating transmitting activity. This interference with the reuptake of norepinephrine and/or serotonin is believed by some to underlie the antidepressant activity of amitriptyline.
Target 4 Description Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Target 4 Synonyms
  1. Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2AAR; Alpha-2 adrenergic receptor subtype C10
Target 4 Gene Name ADRA2A
Target 4 Protein Sequence >Alpha-2A adrenergic receptor 
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Target 4 Number of Residues 450
Target 4 Molecular Weight 48956.3
Target 4 Theoretical pI 10.20
Target 4 GO Classification
Function
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha2-adrenergic receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 4 General Function Involved in alpha2-adrenergic receptor activity
Target 4 Pathways Not Available
Target 4 Reactions Not Available
Target 4 Signals
  • None
Target 4 Transmembrane Regions
  • 34-59
  • 71-96
  • 107-129
  • 152-172
  • 195-217
  • 375-395
  • 410-429
Target 4 Essentiality Non Essential
Target 4 Domain Function PF00001:7tm_1
Target 4 GenBank ID Protein Not Available
Target 4 UniProtKB ID P08913 Link Image
Target 4 Cellular Location Cell membrane
Target 4 Gene Sequence >1353 bp 
ATGGGCTCCCTGCAGCCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGG
GGCGGCGCCCGGGCCACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCC
GGCCTGCTCATGCTGCTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACG
AGCCGCGCGCTCAAGGCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATC
CTGGTGGCCACGCTCGTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTAC
TTCGGCAAGGCTTGGTGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCC
ATCGTGCACCTGTGCGCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAG
TACAACCTGAAGCGCACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATC
TCGGCCGTCATCTCCTTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGC
CCGCAGCCGGCCGAGCCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCG
TGCATCGGCTCCTTCTTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTAC
CAGATCGCCAAGCGTCGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCC
GCGCCGCCGGGGGGCACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGC
CCGGGGGGCGCAGAGGCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCC
GCGCCGGCCGGGCCGCGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGAC
CACGCCGAGCGGCCTCCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAG
GCCCGAGCGAGCCAGGTGAAGCCGGGCGACAGCCTGCCGCGGCGCGGGCCGGGGGCGACG
GGGATCGGGACGCCGGCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCG
CGCTGGCGCGGGCGGCAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATC
GGAGTGTTCGTGGTGTGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGG
TGCTCCGTGCCACGCACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCG
TTGAACCCGGTCATCTACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATC
CTCTGTCGGGGGGACAGGAAGCGGATCGTGTGA
Target 4 GenBank Gene ID Not Available
Target 4 GeneCard ID ADRA2A Link Image
Target 4 GenAtlas ID ADRA2A Link Image
Target 4 HGNC ID HGNC:281 Link Image
Target 4 Chromosome Location Chromosome:10
Target 4 Locus 10q24-q26
Target 4 SNPs SNPJam Report Link Image
Target 4 Toxin References
  • T560 - Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. [PubMed Link Image]
Target 4 General References 2823383; 2568356; 2170371; 10948191; 16567612

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government.