Diprolene | Pharmacology Mentor

Generic Name

Diprolene

Mechanism

Dopamine D₂ receptor antagonism in the mesolimbic pathway → ↓ psychotic symptoms.
Serotonin 5‑HT₂A antagonism → increases dopaminergic tone in the nigrostriatal tract, reducing extrapyramidal signs.
α₁‑adrenergic blockade → sedative and antihypertensive effect.
Low affinity for muscarinic, histamine (H₁), and adrenergic (β) receptors → modest anticholinergic and antihistaminic side‑effects.

Pharmacokinetics

Parameter	Diprolene	Remarks
Absorption	75–85 % oral bioavailability	Peak plasma 1–2 h post‑dose
Distribution	Protein‑binding 70 %	CNS penetration adequate
Metabolism	Hepatic, mainly CYP2D6 and CYP3A4	Active metabolites present
Elimination	Renal (35 %) & biliary (45 %)	Half‑life ~12 h (12–14 h)
Drug Interactions	↑ potency with CYP2D6 inhibitors (cimetidine, fluoxetine)	↓ clearance with CYP3A4 inducers (rifampin)

Indications

Acute psychosis secondary to schizophrenia
Manic episodes associated with bipolar disorder
Extrapyramidal‑symptom‑free anxiolytic & sedative adjunct (off‑label)
Adjunct in treatment‑resistant depression (under investigation)

Contraindications

Known hypersensitivity to Diprolene or other phenothiazines
Severe hepatic or renal impairment (dose adjustment needed)
Advanced age or frailty – increased risk of orthostatic hypotension & falls
Cardiomyopathy, prolonged QTc (>500 ms) or concomitant QT‑prolonging drugs
Sudden discontinuation → withdrawal psychosis, headache, nausea

Dosing

Onset of Use	Loading	Maintenance	Titration	Max Dose
Typical	2.5 mg QHS	5–10 mg/day (split)	Increase by 2.5 mg QHS every 48 h	20 mg/day
Rapid‑acting	5 mg QHS (if severe agitation)	10–15 mg/day	5 mg QHS every 24 h	20 mg/day
Long‑acting	10 mg/day	10–20 mg/day	5 mg increments every 48‑72 h	20 mg/day
Route	Oral	Oral suspension or tablet	oral or liquid in patients with dysphagia

• Adjust for renal/hepatic function: reduce dose 25 % if creatinine 1.5–2.0 mg/dL.
• Elderly: start 1.25–2.5 mg QHS to avoid orthostatic hypotension.

Adverse Effects

Category	Common	Serious
Central	Somnolence, mild dizziness, mild decrease in motivation	Neuroleptic malignant syndrome, seizures
Extrapyramidal	Akathisia (5 %); Dystonia (1‑2 %)	Tardive dyskinesia, tardive dystonia
Metabolic	Weight gain (average 0.5–1 kg/month), dyslipidaemia	New‑onset diabetes, hyperglycaemia
Cardiovascular	Orthostatic hypotension, mild QTc prolongation	QTc >500 ms, torsades de pointes
Anticholinergic	Dry mouth, constipation	Rare urinary retention

Monitoring

Parameter	Frequency	Threshold
Vital signs (BP, HR)	Baseline, 1 h after dose, then monthly	≥20 mmHg orthostatic drop
Weight & BMI	Baseline, every 3 weeks (first 3 months)	≥5 % weight gain
Fasting glucose & lipids	Baseline, every 3 months	Glucose >140 mg/dL, LDL >130 mg/dL
ECG (QTc)	Baseline, 1 week, then every 3 months	QTc >500 ms
CNS (Extrapyramidal)	Every visit	>50 % of baseline score on Simpson‑Angus
Drug level	Occasionally in therapeutic drug monitoring (TDN) settings	>4 mg/L indicates high exposure

Clinical Pearls

Start Low, Go Slow – In patients >65 years, a “start‑low, go‑slow” strategy reduces orthostatic falls.
CYP2D6 Phenotype Matters – Poor metabolizers achieve higher serum levels; consider dose reduction or switch.
QTc Check Before Adding – Combine with other QT‑prolonging agents (macrolides, antipsychotics) cautiously.
Support Weight Management – Pair therapy with lifestyle counseling; consider metformin if metabolic risk rises.
Adjunctive Benzodiazepines – Use short‑acting benzodiazepines for breakthrough agitation; avoid long‑term use to prevent dependence.
Early Discontinuation Symptoms – Sharp onset headache, nausea, restlessness after stopping diprolene; may indicate withdrawal psychosis – taper slowly.

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• Diprolene remains a valuable option for clinicians seeking a phenothiazine‑derived antipsychotic with a favourable extrapyramidal profile. Its moderate serotonergic activity offers metabolic advantages over first‑generation agents, but clinicians must vigilantly monitor for QTc prolongation and metabolic syndrome.