59729-33-8

Citalopram is a specific serotonin-uptake inhibitor useful in the treatment of depression. In endogenous depression citalopram was reported to be as effective as amitriptyline and mianserin, while being inferior to clomipramine in both endogenous and non-endogenous depression.

Oil, boiling point 175-181°C/4.00Pa.
Citalopram Hydrobromide: C20H21FN2O?HBr. [59729-32-7]. Crystallizes from isopropyl alcohol, melting point 182-183°C.
Citalopram Oxalate: C20H21FN2O?C2H2O4. Crystallizes, melting point 164-166°C.

Lundbeck (Denmark)

The invention of citalopram dates back to 1972, when Klaus Bøgesø, a chemist at H. Lundbeck A/S in Denmark, and his team, while searching for new antidepressants, rationally designed and synthesized a compound called 1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxynitrile, based on their previous research on the norepinephrine reuptake inhibitor talopram. They quickly completed a patent application, marking the pharmacological starting point for citalopram as a selective serotonin reuptake inhibitor (SSRI). In the late 1970s, the compound entered a systematic preclinical research phase, and its unique highly selective inhibition of the serotonin transporter (SERT) was gradually confirmed, exhibiting good antidepressant activity in animal models. In the early 1980s, citalopram entered clinical trials. Multiple double-blind controlled studies confirmed its significant efficacy and good tolerability for major depressive disorder. It was finally launched in Denmark in 1989 under the brand name Cipramil®, becoming the first domestically developed SSRI antidepressant in the Nordic market. In the 1990s, H. Lundbeck entered into a collaboration agreement with Forest Laboratories in the United States to jointly advance the registration of citalopram in the US. After a series of clinical trials that met FDA requirements, the drug received FDA approval on July 17, 1998, and officially entered the US market in September of the same year under the brand name Celexa®, quickly becoming one of the fastest-growing antidepressants in terms of prescription volume at the time. With the expiration of the citalopram patent in 2003, several generic drugs were launched, further expanding its global usage. This also spurred the development of its S-enantiomer, escitalopram, which was initiated in 1997 and approved in 2002, becoming Lundbeck's next-generation core antidepressant product.

antidepressant monoamine oxidase inhibitor (MAOIs)

scabicide

ChEBI: A nitrile that is 1,3-dihydro-2-benzofuran-5-carbonitrile in which one of the hydrogens at position 1 is replaced by a p-fluorophenyl group, while the other is replaced by a 3-(dimethylamino)propyl group.

Cipramil

Citalopram (Celexa) has an elimination half-life of 35 hours and is 80% bound to plasma proteins. Of all of the SSRIs it has the least effect on the cytochrome P450 system and has the most favorable profile regarding drug–drug interactions.

Citalopram (Celexa) is a racemic mixture and is very SERTselective. The N-monodemethylated compound is slightlyless potent but is as selective. The aryl substituents are importantfor activity. The ether function is important andprobably interacts with the protonated amino group to givea suitable shape for SERT binding.

Highly selective and potent 5-HT uptake inhibitor with no effect on noradrenalin or dopamine uptake (IC 50 values are 1.8, 8800 and 41000 nM respectively). Has negligible activity at a wide range of receptors and is clinically used as an antidepressant. Also available as part of the Serotonin Uptake Inhibitor Tocriset™ .

SSRI antidepressant:
Depressive illness

Panic disorder

Potentially hazardous interactions with other drugs
Analgesics: increased risk of bleeding with aspirin and NSAIDs; risk of CNS toxicity increased with tramadol.
Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone, disopyramide and dronedarone - avoid.
Antibacterials: possibly increased risk of ventricular arrhythmias with IV erythromycin, moxifloxacin, pentamidine and telithromycin.
Anticoagulants: effect of coumarins possibly enhanced; possibly increased risk of bleeding with dabigatran.
Antidepressants: avoid with MAOIs and moclobemide, increased risk of toxicity; avoid with St John’s wort; possibly enhanced serotonergic effects with dapoxetine and duloxetine; can increase tricyclics antidepressant concentration; increased agitation and nausea with tryptophan; possible increased risk of convulsions with vortioxetine.
Antiepileptics: convulsive threshold lowered.
Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid.
Antimalarials: avoid with artemether/lumefantrine and piperaquine with artenimol; possible increased risk of ventricular arrhythmias with chloroquine and quinine.
Antipsychotics: possibly increased clozapine concentration; increased risk of ventricular arrhythmias with haloperidol and pimozide - avoid.
Antivirals: concentration possibly increased by ritonavir.
Beta-blockers: increased risk of ventricular arrhythmias with sotalol - avoid.
Dopaminergics: avoid with selegiline; increased risk of CNS toxicity with rasagiline.
5 HT1 agonist: increased risk of CNS toxicity - avoid; possibly increased risk of serotonergic effects with naratriptan.
Linezolid: use with care, possibly increased risk of side effects.
Lithium: increased risk of CNS effects.
Methylthioninium: risk of CNS toxicity - avoid if possible.

Citalopram is metabolised by demethylation, deamination, and oxidation to active and inactive metabolites. The demethylation of citalopram to one of its active metabolites, demethylcitalopram, involves the cytochrome P450 isoenzymes CYP3A4 and CYP2C19; the metabolism of citalopram is also partly dependent on CYP2D6. Didemethylcitalopram has also been identified as a metabolite of citalopram. It is excreted mainly via the liver (85%) with the remainder via the kidneys. About 12% is excreted in the urine as unchanged drug.