General
Preferred name
MOXONIDINE
Synonyms
MOXONIDINE HYDROCHLORIDE ()
BDF5895 ()
BDF5895 hydrochloride ()
MOXONIDINE HCl75438-57-2 ()
Moxonidine (hydrochloride) ()
Fisiotens ()
LY-326869 ()
Normatens ()
BDF-5896 ()
LY326869 ()
Physiotens ()
Moxonidina ()
BE-5895 ()
BE5895 ()
BDF5896 ()
Moxonidine HCl ()
P&D ID
PD008988
CAS
75438-57-2
1008754-16-2
75536-04-8
Tags
available
biased GPCR ligand
drug
First approval
1991
Drug indication
Alcohol dependence
Drug Status
approved
investigational
Max Phase
4.0
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
METABOLISM Biotransformation is unimportant [A27139] with 10-20% of moxonidine undergoing oxidation reactions to the primary 4,5-dehydromoxonidine metabolite and a guanidine derivative by opening of the imidazoline ring. [FDA label]; ; The antihypertensive effects of these 4,5-dehydromoxonidine and guanidine metabolites are only 1/10 and 1/100 the effect of moxonidine [FDA Label].; ; Oxidation on either the methyl group (pyrimidine ring) or on the imidazole ring of moxonidine results in the formation of the hydroxylmethyl moxonidine metabolite or the hydroxy moxonidine metabolite [A31315]. The hydroxy moxonidine metabolite can be further oxidized to the dihydroxy metabolite or it can lose water to form the dehydrogenated moxonidine metabolite, which itself can be further oxidized to form an N-oxide [A31315]. Aside from these Phase I metabolites, Phase II metabolism of moxonidine is also evident with the presence of a cysteine conjugate metabolite minus chlorine [A31315]. Nevertheless, the identification of the hydroxy moxonidine metabolite with a high level of dehydrogenated moxonidine metabolite in human urine samples suggests that dehydrogenation from the hydroxy metabolite to the dehydrogenated moxonidine metabolite represents the primary metabolic pathway in humans [A31315].; ; The cytochromes P450 responsible for the metabolism of moxonidine in humans have not yet been determined [A31315].; ; Ultimately, the parent moxonidine compound was observed to be the most abundant component in different biological matrices of urinary excretion samples, verifying that metabolism only plays a modest role in the clearance of moxonidine in humans [A31315].
TOXICITY * Contraindicated due to known hypersensitivity to an ingredient (Physiotens tablets contain lactose), heart failure, severe renal impairment, < 16 years old, >75 years old, bradycardia, severe bradyarrhythmia, sick sinus syndrome, second or third degree atrioventricular block, malignant arrhythmias. [FDA Label]; * Used with caution in patients with history of severe coronary artery disease (CAD), unstable angina, angioneurotic edema. [FDA label]; * Pregnancy Category B3:Avoid use during pregnancy (inadequate data in pregnant woman) and lactation (maternal blood stream transfer to breast milk shown) unless benefit clearly justifies risk. [FDA label]; * Lack of specific therapeutic experience in cases of intermittent claudication, Raynaud's disease, Parkinson's disease, epileptic disorders, gluacoma, and depression suggest moxonidine should not be used in such instances [FDA Label].; * Carcinogenicity and genotoxicity does not appear significant. [FDA label]; * Concurrent administration of other hypotensives or sedative and hypnotics can enhance the hypotensive effect and intensify sedation respectively. [FDA label]; * Avoid concurrent Tricyclic Antidepressant (TCA) use to avoid reduction of monoxidine efficacy. [FDA label]; * Generally well tolerated with dry mouth and headache the most common adverse effects [FDA label]; * Symptoms of overdose correlate with pharmacodynamic properties:hypotension, sedation, orthostatic dysregulation, bradycardia, dry mouth with no specific counter-treatment known. [FDA label]
MOA Stimulation of central alpha 2-adrenergic receptors is associated with sympathoadrenal suppression and subsequent reduction of blood pressure. As this class was further explored it was discovered that sympathoadrenal activity can also be suppressed by a second pathway with a newly discovered drug target specific to imidazolines [A27150]. Specifically, moxonidine binds the imidazoline receptor subtype 1 (I1) and to a lesser extent αlpha-2-adrenoreceptors in the RSV causing a reduction of sympathetic activity, reducing systemic vascular resistance and thus arterial blood pressure. [FDA label]; ; Moreover, since alpha-2-adrenergic receptors are considered the primary molecular target that facilitates the most common side effects of sedation and dry mouth that are elicited by most centrally acting antihypertensives, moxonidine differs from these other centrally acting antihypertensives by demonstrating only low affinity for central alpha-2-adrenoceptors compared to the aforementioned I1-imidazoline receptors [FDA Label].
DESCRIPTION Moxonidine is an α2-adrenoceptor agonist. (GtoPdb)
DESCRIPTION I1 receptor and alpha2-adrenoceptor agonist (I1 > alpha2) (Tocriscreen Plus)
DESCRIPTION Selective alpha2A adrenoreceptor agonist; imidazoline binding site agonist; antihypertensive (LOPAC library)
DESCRIPTION I1 receptor and α2-adrenoceptor agonist (I1 > α2) (Tocriscreen Total)
DESCRIPTION Moxonidine hydrochloride is a mixed agonist of α2-adrenergic receptor (α2AR) and imidazoline-1 receptor(I1R). Its Ki values is 4.2±3.2 nmol/L, 13.0±4.2 nmol/L, 9.5±4.1 nmol/L and 15.6±9.8 nmol/L for I1R, α2AAR, α2BAR and α2CAR, respectively. It is used as antihypertensive agent. It displays 40-fold higher affinity for I1 receptors versus α2-adrenoceptors. It reduced stimulated NE overflow (log EC50: -6.15 +/- 0.14). It has been reported to produce dose-dependent analgesia in multiple acute pain assays and has been reported to potently inhibit the binding of [3H]-clonidine to VLM (ventrolateral medulla) membranes in a dose-dependent manner with the IC50 value of 53 ± 10nM. It has shown low affinity for I2-relative to I1R sites in bovine adrenal medullary cells. (BOC Sciences Bioactive Compounds)
Compound Sets
29
AdooQ Bioactive Compound Library
A11317
BiasDB
Moxonidine
BOC Sciences Bioactive Compounds
moxonidine-hydrochloride-cas-75536-04-8-item-474827
Cayman Chemical Bioactives
25639
ChEMBL Approved Drugs
CHEMBL19236
ChEMBL Drugs
CHEMBL19236
Concise Guide to Pharmacology 2023/24
12574
Drug Repurposing Hub
DrugBank
DB09242
DrugBank Approved Drugs
DB09242
DrugCentral
1856
DrugCentral Approved Drugs
1856
DrugMAP
DMGFB0E
DrugMAP Approved Drugs
DMGFB0E
EU-OPENSCREEN Bioactive Compound Library
EOS100742
Guide to Pharmacology
12574
Ki Database
Moxonidine
LOPAC library
LSP-MoA library (Laboratory of Systems Pharmacology)
CHEMBL19236
Mcule NIBR MoA Box Subset
MCULE-1808465205
MedChem Express Bioactive Compound Library
HY-B0374
HY-B0374A
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
moxonidine
TargetMol Bioactive Compound Library
T1028
Tocriscreen Plus
2282
Tocriscreen Total
External IDs
52
Properties
(calculated by RDKit )
Molecular Weight
241.07
Hydrogen Bond Acceptors
6
Hydrogen Bond Donors
2
Rotatable Bonds
2
Ring Count
2
Aromatic Ring Count
1
cLogP
0.82
TPSA
71.43
Fraction CSP3
0.44
Chiral centers
0.0
Largest ring
6.0
QED
0.75
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target Type
Other Pharmacology
Selectivity
alpha2A
Pathway
GPCR/G protein
Neuronal Signaling
Target
Imidazoline Receptor
ADRA2A, ADRA2B, ADRA2C
Member status
member
MOA
Imidazoline I1 Receptor Agonists
imidazoline receptor agonist
Indication
hypertension
Solubility
100 mM in ethanol
100 mM in DMSO
Source data