**Background**
Psychoses, most notably schizophrenia, are complex psychiatric disorders characterized by distortions in thinking, perception, and emotional responsiveness. A primary pharmacological target for treating these conditions is the dopamine D2 receptor, as overactivity in dopaminergic pathways is closely linked to the positive symptoms of schizophrenia. Long-acting depot preparations are often utilized to ensure consistent therapeutic levels of medication and improve patient compliance. In this context, we will introduce a butyrophenone derivative used for the management of psychoses – Haloperidol decanoate.
**Definition**
Haloperidol decanoate is a depot preparation of haloperidol, a butyrophenone derivative with potent antipsychotic activity that primarily targets D2 receptors. According to the Haloperidol decanoate technical information, this compound is characterized by the molecular formula C31H41ClFNO3 and a molecular weight of 530.11.
**In Vivo Studies**
The Haloperidol decanoate biological activity has been extensively studied in animal models to understand its pharmacokinetic and pharmacodynamic properties. In vivo studies using male Wistar rats have demonstrated that a single intramuscular (i.m.) dose of 38 mg/kg increases the gene expression of pro-inflammatory cytokines, COX-2, and iNOS. This administration also downregulates the transcriptional factor erythroid 2-related factor 2 (Nrf2) and the peroxisome proliferator-activated receptor-gamma coactivator (PCG-1α), while increasing glutamate uptake, GLAST gene expression, and the activities of AChE and GPx. Furthermore, pharmacokinetic data using [14C]haloperidol decanoate (34.25 mg/0.18 ml of sesame oil containing 1.5% benzyl alcohol, i.m., single dose) revealed the highest levels of total radioactivity and the compound in the plasma and examined lymph nodes of male Wistar rats. Additionally, a single subcutaneous (s.c.) dose of 100 mg/kg significantly increases the B max of [3H]spiperone binding in the striatum of rat models. Beyond its neurological effects, Haloperidol decanoate in vivo administration has been shown to reduce intestinal transport, increase gastric emptying, and reduce acid output in rats. In conclusion, Haloperidol decanoate is a long-acting antipsychotic agent that modulates dopaminergic activity and induces various neuroinflammatory and physiological responses.
Keywords
Haloperidol decanoate, 74050-97-8, Dopamine Receptor, COX, NO Synthase, Cyclooxygenase, Nitric oxide synthases, NOS, antipsychotic activity, schizophrenia, schizoaffective disorder, Inhibitor, inhibitor, inhibit
References
[1] R Beresford, et al. Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis. Drugs. 1987 Jan;33(1):31-49.
[2] Schmitz, I., et al., (2025). A single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation: focus on the glial response. Pharmacological reports : PR, 77(3), 800–808.
[3] Oh-e, Y., et al., (1991). Pharmacokinetics of haloperidol decanoate in rats. Journal of pharmacobio-dynamics, 14(11), 615–622.
[4] Akiyama, K., et al., (1987). Effect of chronic administration of haloperidol (intermittently) and haloperidol-decanoate (continuously) on D2 dopamine and muscarinic cholinergic receptors and on carbachol-stimulated phosphoinositide hydrolysis in the rat striatum. The Japanese journal of psychiatry and neurology, 41(2), 311–320.