DT-Web

DB04948 - Lofexidine


Identification
Name Lofexidine
Accession Number DB04948
Type small molecule
Description Lofexidine is an alpha2-adrenergic receptor agonist. It can be used as a short acting anti-hypertensive, but is mostly used to help relieve symptoms of heroin or opiate withdrawal in opiate dependency. It is approved in the United Kingdom, but is still undergoing clinical trials in the United States.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 259.132
Groups approved
Monoisotopic Weight 258.03266843
Pharmacology
Indication Investigated for use/treatment in addictions and substance abuse.
Mechanism of action Lofexidine is an alpha2-adrenergic receptor agonist.
Absorption Lofexidine is extensively absorbed and achieves peak plasma concentration at 3 hours after administration of a single dose. Bioavailability is over 90% following oral administration.
Protein binding 80 to 90%
Biotransformation Lofexidine undergoes extensive metabolism in the liver and excretion is mainly by the kidney.
Route of elimination Not Available
Toxicity Lofexidine was tolerated at high dosage in singe dose toxicity studies in animals, the LD50 being >77 mg/kg. With repeat dosing in mice, rats and dogs symptoms related to the pharmacology of the drug (ataxia, sedation, tremor, unkempt appearance and exhaustion) appeared. Overdosage may cause hypotension, bradycardia and sedation.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Alpha-2A adrenergic receptor
Name Alpha-2A adrenergic receptor
Gene Name ADRA2A
Pharmacological action yes
Actions agonist
References
  • Jin Y, Verstappen A, Elko E, Cammarata P, Yorio T: Effects of lofexidine, an alpha 2-adrenoreceptor agonist, on ocular blood flow and ion transport of rabbit iris-ciliary body. J Ocul Pharmacol. 1992 Spring;8(1):23-33. - Pubmed
  • Strang J, Bearn J, Gossop M: Lofexidine for opiate detoxification: review of recent randomised and open controlled trials. Am J Addict. 1999 Fall;8(4):337-48. - Pubmed
  • Erb S, Hitchcott PK, Rajabi H, Mueller D, Shaham Y, Stewart J: Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking. Neuropsychopharmacology. 2000 Aug;23(2):138-50. - Pubmed
DTHybrid score 0.239

Predictions


Id Partner name Gene Name Score
556 Alpha-1A adrenergic receptor ADRA1A 0.093
378 Alpha-2C adrenergic receptor ADRA2C 0.0602
629 Alpha-2B adrenergic receptor ADRA2B 0.0592
23 D(1A) dopamine receptor DRD1 0.0376
502 5-hydroxytryptamine 2A receptor HTR2A 0.0354
4512 Cytochrome P450 3A4 CYP3A4 0.0296
632 Alpha-1B adrenergic receptor ADRA1B 0.0276
320 5-hydroxytryptamine 1A receptor HTR1A 0.0276
4200 Cytochrome P450 1A2 CYP1A2 0.0272
4119 Cytochrome P450 2D6 CYP2D6 0.0272
590 5-hydroxytryptamine 2C receptor HTR2C 0.0261
831 D(2) dopamine receptor DRD2 0.0251
725 5-hydroxytryptamine 1D receptor HTR1D 0.023
163 D(1B) dopamine receptor DRD5 0.0228
885 5-hydroxytryptamine 1B receptor HTR1B 0.0211
492 Histamine H1 receptor HRH1 0.0203
638 D(3) dopamine receptor DRD3 0.019
432 D(4) dopamine receptor DRD4 0.0177
789 Alpha-1D adrenergic receptor ADRA1D 0.0169
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0166
824 Sodium-dependent serotonin transporter SLC6A4 0.0166
766 Beta-2 adrenergic receptor ADRB2 0.0162
436 5-hydroxytryptamine 2B receptor HTR2B 0.016
716 5-hydroxytryptamine 7 receptor HTR7 0.0142
193 Beta-1 adrenergic receptor ADRB1 0.0137
713 Sodium-dependent dopamine transporter SLC6A3 0.0132
3941 Amine oxidase [flavin-containing] A MAOA 0.0122
1588 Multidrug resistance protein 1 ABCB1 0.0118
131 Synaptic vesicular amine transporter SLC18A2 0.0118
3810 Catechol O-methyltransferase COMT 0.0083
6070 Nischarin NISCH 0.0075
4757 Cytochrome P450 2C9 CYP2C9 0.0074
4118 Cytochrome P450 3A5 CYP3A5 0.007
709 ATP-sensitive inward rectifier potassium channel 1 KCNJ1 0.0068
6147 Solute carrier family 22 member 3 SLC22A3 0.0067
6145 Solute carrier family 22 member 1 SLC22A1 0.0066
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0066
1517 Beta-3 adrenergic receptor ADRB3 0.0063
1539 Oligopeptide transporter, small intestine isoform SLC15A1 0.0063
6020 Aldehyde oxidase AOX1 0.0062
3939 Amine oxidase [flavin-containing] B MAOB 0.0061
6030 Cytochrome P450 2B6 CYP2B6 0.0061
6016 Cytochrome P450 2C19 CYP2C19 0.0059
274 Muscarinic acetylcholine receptor M5 CHRM5 0.0059
341 5-hydroxytryptamine 3 receptor HTR3A 0.0058
828 Phenylalanine-4-hydroxylase PAH 0.0058
3109 Phenylalanine-4-hydroxylase phhA 0.0058
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0057
1256 5-hydroxytryptamine 6 receptor HTR6 0.0056
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0056
6144 Solute carrier family 22 member 2 SLC22A2 0.0055
118 Organic cation/carnitine transporter 2 SLC22A5 0.0054
6024 Cytochrome P450 1A1 CYP1A1 0.0052
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0051
617 Muscarinic acetylcholine receptor M2 CHRM2 0.005
6013 Cytochrome P450 2E1 CYP2E1 0.0049
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0048
6107 Cytochrome P450 3A7 CYP3A7 0.0047
3426 Glutamine synthetase glnA 0.0047
3987 Glutamine synthetase GLUL 0.0047
3923 Cholinesterase BCHE 0.0046
124 Histamine H2 receptor HRH2 0.0046
528 5-hydroxytryptamine 1E receptor HTR1E 0.0046
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0042
4120 NADPH--cytochrome P450 reductase POR 0.0037
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0032
1636 Trace amine-associated receptor 1 TAAR1 0.0027
696 Kappa-type opioid receptor OPRK1 0.0026
6164 POU domain, class 5, transcription factor 1 POU5F1 0.0023
465 Calmodulin CALM1 0.0023
4924 Cytochrome P450 2C8 CYP2C8 0.0022
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0022
1656 CYP2B protein CYP2B 0.0021
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0019
233 Potassium channel subfamily K member 2 KCNK2 0.0017
587 Serum albumin ALB 0.0017
833 Organic cation/carnitine transporter 1 SLC22A4 0.0017
6151 Monocarboxylate transporter 10 SLC16A10 0.0016
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0015
4112 Voltage-dependent L-type calcium channel subunit beta-4 CACNB4 0.0015
4114 Voltage-dependent L-type calcium channel subunit beta-3 CACNB3 0.0015
4113 Voltage-dependent L-type calcium channel subunit alpha-1F CACNA1F 0.0014
333 Voltage-dependent L-type calcium channel subunit beta-1 CACNB1 0.0013
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0013
158 Sodium channel protein type 1 subunit alpha SCN1A 0.0013
4110 Voltage-dependent L-type calcium channel subunit beta-2 CACNB2 0.0011
4115 Voltage-dependent L-type calcium channel subunit alpha-1D CACNA1D 0.0011
4111 Voltage-dependent L-type calcium channel subunit alpha-1S CACNA1S 0.0011
478 Voltage-dependent L-type calcium channel subunit alpha-1C CACNA1C 0.0011
1618 High affinity nerve growth factor receptor NTRK1 0.001
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.001
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.001
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.001
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.001
164 Histamine H4 receptor HRH4 0.0009
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0008
467 Delta-type opioid receptor OPRD1 0.0007
1898 Cytochrome P450 1B1 CYP1B1 0.0005
5718 Cytochrome P450 2A6 CYP2A6 0.0005
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