アモキサピン

3.4

3.71

1.71e-01 g/L

34.4 [ug/mL] (The mean of the results at pH 7.4)

Antidepressants -> Tricyclic antidepressants (TCA)

Breast Feeding; Lactation; Milk, Human; Antidepressive Agents; Serotonin Uptake Inhibitors

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

175-176

175.5 °C

8.71

8.7

172.3 Ų [M+H]+ [CCS Type: DT; Buffer gas: N2; Ionization: ESI+; Dataset: Antidepressants]

170.2 Ų [M+H]+ [CCS Type: TW; Method: Major Mix IMS/Tof Calibration Kit (Waters)]

165.42 Ų [M+K]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

171.2 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 45 reports by companies from 2 notifications to the ECHA C&L Inventory.

Hazard Traits - Developmental Toxicity

Dibenzb,f1,4oxazepine, 2-chloro-11-(1-piperazinyl)-: Does not have an individual approval but may be used under an appropriate group standard

Treatment of amoxapine overdosage should be symptomatic and supportive, but with special attention to prevention or control of seizures. If the patient is conscious, induced emesis followed by gastric lavage with appropriate precautions to prevent pulmonary aspiration should be accomplished as soon as possible. Following lavage, activated charcoal may be administered to reduce absorption, and repeated administrations may facilitate drug elimination. An adequate airway should be established in comatose patients and assisted ventilation instituted if necessary. Seizures may respond to standard anticonvulsant therapy such as intravenous diazepam and/or phenytoin. The value of physostigmine appears less certain. Status epilepticus, should it develop, requires vigorous treatment. (L1712)

Liver test abnormalities occur in a small proportion of patients on long term therapy with amoxapine, but elevations are usually mild, asymptomatic and transient, reversing even with continuation of medication. Instances of clinically apparent acute liver injury without jaundice have been reported due to amoxapine, but have been quite rare. Published cases have been mild, anicteric and asymptomatic. The onset of injury was within 1 to 4 weeks of starting, and the pattern of serum enzyme elevations was hepatocellular. Immunoallergic features and autoantibody formation were not present.

The common adverse effects of amoxapine therapy include, but are not limited to, insomnia, palpitations, tachycardia, hypotension, and constipation. Furthermore, research has indicated that amoxapine may trigger hypomanic states in individuals with underlying bipolar disorder. Amoxapine has been observed to induce noradrenaline-mediated contraction of the urethra in guinea pigs and rats in various laboratory studies, leading to elevated urethral resistance. In addition, the drug has been associated with instances of painful ejaculations relieved by the administration of tamsulosin. Notably, tricyclic antidepressants (TCAs), including amoxapine, are correlated with an increased risk of seizures, especially in older patients and those with epilepsy. Therefore, it is recommended to use SSRIs or SNRIs in patients with a history of epilepsy and seizures.

Signs and Symptoms of Overdose

Amoxapine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT).

Toxic manifestations of amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects, particularly grand mal convulsions, occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial amoxapine overdosage in some cases. Renal failure may develop two to five days after toxic overdose in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomuolysis and myolobinurla is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Amoxapine

Ambiguous-DILI-concern

3

Adverse reactions

DOI:10.1016/j.drudis.2016.02.015

N - Nervous system

QN - Nervous system

Amoxapine is a tricyclic antidepressant of the dibenzoxazepine class, chemically distinct from the dibenzodiazepines, dibenzocycloheptenes, and dibenzoxepines. It has a mild sedative component to its action. The mechanism of its clinical action in man is not well understood. In animals, amoxapine reduced the uptake of nor-epinephirine and serotonin and blocked the response of dopamine receptors to dopamine. Amoxapine is not a monoamine oxidase inhibitor. Clinical studies have demonstrated that amoxapine has a more rapid onset of action than either amitriptyline or imipramine

Amoxapine is almost completely metabolized in the liver to its major metabolite, 8-hydroxyamoxapine, and a minor metabolite, 7-hydroxyamoxapine. Both metabolites are phamacologically inactive and have half-lives of approximately 30 and 6.5 hours, respectively.

Amoxapine is almost completely metabolized in the liver to its major metabolite, 8-hydroxyamoxapine, and a minor metabolite, 7-hydroxyamoxapine. Both metabolites are phamacologically inactive and have half-lives of approximately 30 and 6.5 hours, respectively. Route of Elimination: 60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine. Half Life: 8 hours

R63VQ857OT

AMOXAPINE

Established Pharmacologic Class [EPC] - Tricyclic Antidepressant

Amoxapine is a Tricyclic Antidepressant.

AMOXAPINE

Tricyclic Antidepressant [EPC]

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However, the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system.

Drugs that inhibit the transport of neurotransmitters into axon terminals or into storage vesicles within terminals. For many transmitters, uptake determines the time course of transmitter action so inhibiting uptake prolongs the activity of the transmitter. Blocking uptake may also deplete available transmitter stores. Many clinically important drugs are uptake inhibitors although the indirect reactions of the brain rather than the acute block of uptake itself is often responsible for the therapeutic effects.

Drugs that bind to but do not activate DOPAMINE RECEPTORS, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (ANTIPSYCHOTIC AGENTS) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as ANTIEMETICS, in the treatment of Tourette syndrome, and for hiccup. Dopamine receptor blockade is associated with NEUROLEPTIC MALIGNANT SYNDROME.

Drugs that block the transport of adrenergic transmitters into axon terminals or into storage vesicles within terminals. The tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC) and amphetamines are among the therapeutically important drugs that may act via inhibition of adrenergic transport. Many of these drugs also block transport of serotonin.

Compounds that specifically inhibit the reuptake of serotonin in the brain.

Rapidly and almost completely absorbed from the GI tract. Peak plasma concentrations occur within 1-2 hours of oral administration of a single dose.

60-69% of a single orally administered dose of amoxapine is excreted in urine, principally as conjugated metabolites. 7-18% of the dose is excrete feces mainly as unconjugated metabolites. Less than 5% of the dose is excreted as unchanged drug in urine.

Widely distributed in body tissues with highest concentrations found in lungs, spleen, kidneys, heart, and brain. Lower concentrations can be detected in testes and muscle.