Amoxapine

ASENDIN

Open Amoxapine in the interactive console ↗

Pronunciation: a-MOX-a-peen

Amoxapine ballicule: receptor binding, kinetics and half-life diagram — Mechanism of action: Amoxapine ballicule

Amoxapine ASENDIN mascot mnemonic cartoon — Visual mnemonic: Amoxapine mascot
**“Ammo mocks A send-in”**
Tricycle symbol → tricyclic antidepressant (TCA)
Spooky mascot → D2-blocking like an antipsychotic
He’s ascendin’ and holding a “send-in”

What it isTricyclic antidepressant that is also a D2 antagonist; active metabolite of loxapine.

Why it mattersIt combines antidepressant and antipsychotic action in one molecule.

What it changes⚑ The D2 blockade brings extrapyramidal effects, tardive dyskinesia and neuroleptic malignant syndrome — unexpected from a tricyclic.

Amoxapine molecular structure (skeletal formula) — Molecular structure: Amoxapine

FDA-approved for

depression (~1980)

FDA label

Read the full label on DailyMed ↗

BOXED WARNING Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with antidepressant use.

FDA dosing	Population	Start	Target	Max
Depression	Adult	50 mg BID-TID	200-300 mg/day	400 mg/day (600 mg/day in hospitalized refractory patients)
Depression	Elderly	25 mg BID-TID	100-150 mg/day	300 mg/day

Titration Maintain 300 mg/day for at least 2 weeks before increasing above 300 mg/day.

Renal Undefined

Hepatic Undefined

Instructions

Doses over 300 mg/day must be given in divided doses
When effective dose is established, may give as single dose (not exceeding 300 mg) at bedtime

Available strengths

tab 25, 50, 100, 150 mg

Contraindications

MAOIs (concurrently or within 14 days) due to risk of hyperpyretic crises, severe convulsions, and death
Acute recovery phase following myocardial infarction

Cautions

Tardive dyskinesia
Neuroleptic malignant syndrome
Seizures
Sedative and anticholinergic effects

Adverse reactions

Drowsiness
Dry mouth
Constipation
Blurred vision

Pregnancy No teratogenic effect in animals; embryotoxicity and fetotoxic effects (intrauterine death, stillbirth, decreased birth weight) seen in animals at 3-10x human dose.

Lactation Undefined

Cost

Amoxapine (ASENDIN)

Strength		#/mo	CostPlus
25 mg	tab	60 BID	offered
50 mg	tab	60 BID	offered
100 mg	tab	60 BID	offered
150 mg	tab	60 BID	offered

NADAC is a voluntary CMS survey of what retail community pharmacies pay for the drugs they stock. Amoxapine is dispensed outside retail pharmacies, so it rarely appears on surveyed invoices.

Generic entry1989

⚠ BOXED WARNING

Suicidal thoughts and behaviors in patients under 25

Classes and tags

Clinical profile

Therapeutic safety burden3 / 4

Overdose danger4 / 4

Weight-gain liability1 / 4

Sedation liability1 / 4

QT / Torsades1 / 4

Direct muscarinic antagonism0 / 4

Embryofetal risk2 / 4

Legacy pregnancy categoryC

Defining liabilitySeizures, coma, arrhythmia and neuroleptic-like toxicity make overdose especially dangerous.

Serotonicity

This drug is routinely called serotonergic. By Gillman’s human-effect criteria it does not raise serotonin in the synapse.

No established clinically meaningful SRI mechanism; confidence is lower than for the classic Gillman-reviewed TCAs.

Label contraindicationMAOIs (concurrently or within 14 days) due to risk of hyperpyretic crises, severe convulsions, and death. The label governs prescribing; Gillman’s point concerns serotonin toxicity only.

It binds the serotonin transporter, and its SERT peg is drawn to that textbook affinity. The pale halo around the peg marks binding that, by Gillman’s human-effect criteria, does not produce clinical serotonin reuptake inhibition.

Gillman’s four human testsA measurable SERT affinity that fails all four is not clinical serotonicity.