General
Preferred name
ZOLPIDEM
Synonyms
Ambien ()
SL-800750-23N ()
Stilnoct ()
Ambien / Stilnox ()
ZOLPIDEM TARTRATE ()
[3H]zolpidem ()
Zolpidem civ ()
Sanval ()
Tovalt Odt ()
SL-80.0750-23N ()
Ambien Cr ()
Zolpimist ()
Intermezzo ()
Edluar ()
Myslee ()
Zolpidem tartrate civ ()
SL 80.0750-23N ()
Tovalt ()
Niotal ()
SL-80.0750 ()
Ivadal ()
Zolpidem hemitartrate ()
Stilnox ()
Zolpidem-d6 ()
Zolpidem-d6 (CRM) ()
Zolpidem (CRM) ()
P&D ID
PD000906
CAS
959605-90-4
103188-50-7
82626-48-0
Tags
natural product
drug
available
Approved by
FDA
First approval
1992
Drug Status
approved
Drug indication
Sedative-Hypnotic
Insomnia
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
HALF-LIFE
The average zolpidem elimination half-life was 2.6 and 2.5 hours, for the 5 and 10 mg tablets, respectively [FDA label].
ABSORPTION
Zolpidem is rapidly absorbed from the gastrointestinal tract. In a single-dose crossover study in 45 healthy subjects given 5 and 10 mg zolpidem tartrate tablets, the average peak zolpidem concentrations (Cmax) were 59 and 121 ng/mL, respectively, occurring at a mean time (Tmax) of 1.6 hours for both doses [FDA label].
INDICATION
This drug is indicated for the short-term treatment of insomnia in adults characterized by difficulties with sleep initiation [FDA label].
ROE
Zolpidem tartrate tablets are converted to inactive metabolites that are eliminated mainly by renal excretion [FDA label].
METABOLISM
Zolpidem is metabolized to three pharmacologically by various hepatic cytochrome P450 (CYP) isoenzymes, mainly CYP3A4, but also CYP1A2 and CYP2C9 [A175429], [A175447]. Although zolpidem is heavily metabolized, all three metabolites are inactive [A175426]. The major metabolic routes in humans are oxidation of the methyl group on the phenyl ring or the methyl group on the imidazopyridine moiety, to produce carboxylic acids (metabolites I and II), and hydroxylation of one of the imidazopyridine groups (to produce metabolite X). Another less common pathway is by the oxidation of the methyl groups on the substituted amide [A175429].
METABOLISM
Zolpidem is metabolized to three pharmacologically by various hepatic cytochrome P450 (CYP) isoenzymes, mainly CYP3A4, but also CYP1A2 and CYP2C9 [A175429], [A175447].; Although zolpidem is heavily metabolized, all three metabolites are inactive [A175426]. ; ; The major metabolic routes in humans are oxidation of the methyl group on the phenyl ring or the methyl group on the imidazopyridine moiety, to produce carboxylic acids (metabolites I and II), and hydroxylation of one of the imidazopyridine groups (to produce metabolite X). Another less common pathway is by the oxidation of the methyl groups on the substituted amide [A175429].
MOA
Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with a _GABA-BZ_ receptor complex and shares various pharmacological properties with the _benzodiazepine_ class of drugs [FDA label]. Subunit binding of the _GABAA_ receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of zolpidem. The main regulatory site of the GABAA receptor complex can be found on its _alpha (α) subunit_ and is called the _benzodiazepine_ (BZ) or _omega (Ï)_ receptor. At least three different subtypes of the (Ï) receptor have been identified to this date [FDA label]. In contrast to benzodiazepine drugs, which are found to modulate all benzodiazepine receptor subtypes in a non-selective fashion, zolpidem binds the (BZ1) receptor specifically with a potent affinity for the alpha 1/alpha 5 subunits (in vitro) [FDA label]. More recent studies suggest that zolpidem binds primarily to the alpha 1, 2, and 3 subunits of the GABA receptor [A173896], [A10523], [A175567], and not the alpha 5 subunit. The (_BZ1_) receptor is found primarily on the Lamina IV of the brain sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. Specific and selective binding of zolpidem on the (BZ1) receptor is not considered absolute, however, this binding could potentially explain the relative lack of myorelaxant and anticonvulsant activity in animal studies in addition to the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses [FDA label].
TOXICITY
Oral (male rat) LD50 = 695 mg/kg [MSDS]. **Overdose** Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma, in addition to cardiorespiratory collapse resulting in fatal outcomes have been reported [FDA label]. **Withdrawal effects** Following rapid decreases in dose or abrupt discontinuation of zolpidem and other sedative/hypnotics, reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs have been made [FDA label]. **Carcinogenesis** Zolpidem was administered to rats and mice over a span of 2 years at dietary dosages of 4, 18, and 80 mg/kg/day. In mice, these doses are considered 26 to 520 times or 2 to 35 times the maximum 10 mg human dose, respectively. In rats, these doses are 43 to 876 times or 6 to 115 times the maximum 10 mg human dose. No evidence of carcinogenicity was seen in mice. Renal liposarcomas were observed in 4/100 rats (3 males, 1 female) receiving 80 mg/kg/day, and a renal lipoma was observed in one male rat at the 18 mg/kg/day dose. Incidence rates of lipoma and liposarcoma for zolpidem were similar to those seen in historical control cases, and the tumor findings are presumed to be a spontaneous occurrence, not causally related to zolpidem [FDA label]. **Mutagenesis** Zolpidem did not show mutagenic activity in several tests including the Ames test, genotoxicity in mouse lymphoma cells in vitro, chromosomal aberrations in cultured human lymphocytes, abnormal DNA synthesis in rat hepatocytes in vitro, and the micronucleus test performed in mice [FDA label]. **Impairment of fertility** In a rat reproduction study, the high dose (100 mg base/kg) of zolpidem lead to irregular estrus cycles and prolonged precoital intervals, however, there was no effect on male or female fertility after daily oral doses comparable to 5 to 130 times the recommended human dose. No effects on any other fertility parameters were observed [FDA label]. **Use in pregnancy** This drug is considered a pregnancy category C drug. There are currently no sufficient conclusive studies completed in pregnant women to determine the safety of zolpidem use during pregnancy. Zolpidem should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus. **Use in nursing** From 0.004% to 0.019% of the total administered zolpidem dose is excreted into milk. The effect of zolpidem on the nursing infant is unknown at this time. Caution should be observed when zolpidem is administered to a nursing mother [FDA label].
MOA
Zolpidem, the active moiety of zolpidem tartrate, is a hypnotic substance with a chemical structure that is not related to the structure benzodiazepines, barbiturates, pyrrolopyrazines, pyrazolopyrimidines or other drugs exerting hypnotic effects. It interacts with a _GABA-BZ_ receptor complex and shares various pharmacological properties with the _benzodiazepine_ class of drugs [FDA label].; ; Subunit binding of the _GABAA_ receptor chloride channel macromolecular complex is thought to lead to the sedative, anticonvulsant, anxiolytic, and myorelaxant drug effects of zolpidem. The main regulatory site of the GABAA receptor complex can be found on its _alpha (α) subunit_ and is called the _benzodiazepine_ (BZ) or _omega (Ï)_ receptor. At least three different subtypes of the (Ï) receptor have been identified to this date [FDA label].; ; In contrast to benzodiazepine drugs, which are found to modulate all benzodiazepine receptor subtypes in a non-selective fashion, zolpidem binds the (BZ1) receptor specifically with a potent affinity for the alpha 1/alpha 5 subunits (in vitro) [FDA label]. More recent studies suggest that zolpidem binds primarily to the alpha 1, 2, and 3 subunits of the GABA receptor [A173896], [A10523], [A175567], and not the alpha 5 subunit. ; ; The (_BZ1_) receptor is found primarily on the Lamina IV of the brain sensorimotor cortical regions, substantia nigra (pars reticulata), cerebellum molecular layer, olfactory bulb, ventral thalamic complex, pons, inferior colliculus, and globus pallidus. Specific and selective binding of zolpidem on the (BZ1) receptor is not considered absolute, however, this binding could potentially explain the relative lack of myorelaxant and anticonvulsant activity in animal studies in addition to the preservation of deep sleep (stages 3 and 4) in human studies of zolpidem at hypnotic doses [FDA label].
TOXICITY
Oral (male rat) LD50 = 695 mg/kg [MSDS]. ; ; **Overdose**; ; Symptoms of overdose include impairment of consciousness ranging from somnolence to light coma, in addition to cardiorespiratory collapse resulting in fatal outcomes have been reported [FDA label].; ; **Withdrawal effects**; ; Following rapid decreases in dose or abrupt discontinuation of zolpidem and other sedative/hypnotics, reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs have been made [FDA label]. ; ; **Carcinogenesis**; ; Zolpidem was administered to rats and mice over a span of 2 years at dietary dosages of 4, 18, and 80 mg/kg/day. In mice, these doses are considered 26 to 520 times or 2 to 35 times the maximum 10 mg human dose, respectively. In rats, these doses are 43 to 876 times or 6 to 115 times the maximum 10 mg human dose. No evidence of carcinogenicity was seen in mice. Renal liposarcomas were observed in 4/100 rats (3 males, 1 female) receiving 80 mg/kg/day, and a renal lipoma was observed in one male rat at the 18 mg/kg/day dose. Incidence rates of lipoma and liposarcoma for zolpidem were similar to those seen in historical control cases, and the tumor findings are presumed to be a spontaneous occurrence, not causally related to zolpidem [FDA label].; ; **Mutagenesis**; ; Zolpidem did not show mutagenic activity in several tests including the Ames test, genotoxicity in mouse lymphoma cells in vitro, chromosomal aberrations in cultured human lymphocytes, abnormal DNA synthesis in rat hepatocytes in vitro, and the micronucleus test performed in mice [FDA label].; ; **Impairment of fertility**; ; In a rat reproduction study, the high dose (100 mg base/kg) of zolpidem lead to irregular estrus cycles and prolonged precoital intervals, however, there was no effect on male or female fertility after daily oral doses comparable to 5 to 130 times the recommended human dose. No effects on any other fertility parameters were observed [FDA label]. ; ; **Use in pregnancy**; ; This drug is considered a pregnancy category C drug. There are currently no sufficient conclusive studies completed in pregnant women to determine the safety of zolpidem use during pregnancy. Zolpidem should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.; ; **Use in nursing**; ; From 0.004% to 0.019% of the total administered zolpidem dose is excreted into milk. The effect of zolpidem on the nursing infant is unknown at this time. Caution should be observed when zolpidem is administered to a nursing mother [FDA label].
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
26
ChEMBL Approved Drugs
ChEMBL Drugs
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
DrugMatrix
Ki Database
LSP-MoA library (Laboratory of Systems Pharmacology)
Mcule NIBR MoA Box Subset
Natural product-based probes and drugs
NCATS Inxight Approved Drugs
NIH Clinical Collections (NCC)
Novartis Chemogenetic Library (NIBR MoA Box)
NPC Screening Collection
ReFrame library
The Spectrum Collection
ZINC Tool Compounds
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
68
Molecular Weight
307.17
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
0
Rotatable Bonds
3
Ring Count
3
Aromatic Ring Count
3
cLogP
3.25
TPSA
37.61
Fraction CSP3
0.26
Chiral centers
0.0
Largest ring
6.0
QED
0.74
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Member status
virtual
MOA
GABA(A) BZ Site 1 (Omega-1) Receptor Agonists
Therapeutic Indication
Hypnotic
Therapeutic Class
CNS & PNS
Source data
