Pimozide is a synthetic diphenylbutylpiperidine antipsychotic active pharmaceutical ingredient with established pharmaceutical use in the management of Tourette’s disorder. Pimozide CAS Number 2062-78-4 identifies the active substance, which has the molecular formula C28H29F2N3O and a molecular weight of 461.55 g/mol. FDA GSRS identifies the substance by UNII 1HIZ4DL86F, while PubChem reports a molecular weight of approximately 461.5 g/mol.
Pimozide belongs to the diphenylbutylpiperidine class and produces its principal pharmacological activity through antagonism of central dopaminergic receptors. Current U.S. labeling describes pimozide as an orally active antipsychotic agent and states that its ability to suppress motor and phonic tics in Tourette’s disorder is thought to be related to dopaminergic receptor blockade.
The API is a white to almost white powder according to the Indian Pharmacopoeia monograph. It is highly lipophilic, with a reported XLogP3 value of 6.3, and has very low aqueous solubility. U.S. labeling reports pimozide's solubility in water as less than 0.01 mg/mL, while PubChem reports experimental solubility data around 10 mg/L at 25°C. These values are consistent with its classification as a poorly water-soluble drug substance.
Pimozide has a complex structure containing two fluorophenyl groups, a piperidine ring, and a benzimidazolinone moiety. It has no defined stereocenters, making specific-rotation testing generally not applicable as a routine API identity or purity parameter. PubChem reports 7 rotatable bonds, 4 hydrogen-bond acceptors, 1 hydrogen-bond donor, and a topological polar surface area of 35.6 Ų.
The API's high lipophilicity and low water solubility are important considerations in pharmaceutical formulation. Pimozide is slightly soluble in most organic solvents according to U.S. labeling, while pharmacopoeial descriptions characterize it as practically insoluble in water, sparingly soluble in methanol, and slightly soluble in ethanol (96%).
| Product Parameter | Pimozide |
|---|---|
| Product Name | Pimozide |
| CAS Number | 2062-78-4 |
| UNII | 1HIZ4DL86F |
| Molecular Formula | C28H29F2N3O |
| Molecular Weight | 461.55 g/mol |
| Exact Mass | 461.22786888 Da |
| PubChem CID | 16362 |
| XLogP3 | 6.3 |
| Hydrogen Bond Donors | 1 |
| Hydrogen Bond Acceptors | 4 |
| Rotatable Bonds | 7 |
| Topological Polar Surface Area | 35.6 Ų |
| Defined Stereocenters | 0 |
| Appearance | White to almost white powder |
| Water Solubility | <0.01 mg/mL |
| Melting Point | 216–220°C in IP/Ph. Eur. reporting |
| Pharmacological Class | Antipsychotic / dopamine receptor antagonist |
Pimozide is primarily used as an antipsychotic drug and has a specific established application in the suppression of motor and phonic tics associated with Tourette’s disorder. Its therapeutic activity is principally associated with dopamine receptor blockade in the central nervous system.
The pharmaceutical significance of pimozide also makes control of its chemical purity important. Because the substance has a complex aromatic and heterocyclic structure, related substances can arise from changes in the fluorinated phenyl groups, piperidine-containing portion, unsaturation, oxidation, or other synthetic and degradation pathways.
Pimozide is available in pharmaceutical tablet dosage forms. U.S. labeling identifies 1 mg and 2 mg tablets, while the Indian Pharmacopoeia 2010 entry describes tablet strengths of 1 mg, 2 mg, and 4 mg. These dosage-form specifications should not be confused with the specifications for the bulk API.
Pimozide has particularly useful numerical specifications in the USP 2025 monograph. USP defines pimozide as containing NLT 98.0% and NMT 102.0%, calculated on the dried basis. The current USP analytical procedure uses liquid chromatography with UV detection at 280 nm.
The USP monograph also establishes residue on ignition NMT 0.2% and loss on drying NMT 0.5%. The related-substance procedure controls several named impurities at NMT 0.5% each, unspecified individual impurities at NMT 0.10%, and total impurities at NMT 1.0%.
The Indian Pharmacopoeia provides an additional numerical reference: pimozide contains 99.0–101.0% of C28H29F2N3O calculated on the dried basis, with melting point 216–220°C. IP 2010 also specifies sulfated ash at NMT 0.1%.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | 98.0% – 102.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.2% |
| Individual Impurity | NMT 0.5% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |