17321-77-6 Usage
Description
Clomipramine hydrochloride, also known as Anafranil, is a tricyclic antidepressant and a 3-chlorinated derivative of imipramine. It is an off-white solid and is up to 50 times as potent as imipramine in some bioassays. Clomipramine hydrochloride potently inhibits serotonin and norepinephrine reuptake and acts as an antagonist at histamine, muscarinic acetylcholine, α1-adrenergic, and dopamine receptors.
Uses
Used in Pharmaceutical Industry:
Clomipramine hydrochloride is used as a potent, selective 5-HT uptake blocker for the treatment of depression and obsessive-compulsive disorder. It functions as a serotonin reuptake inhibitor and an antidepressant, helping to alleviate symptoms of anxiety and depression.
Used in Mental Health Treatment:
Clomipramine hydrochloride is used as an anti-depressant and serotonin uptake inhibitor for the management of obsessive-compulsive disorder, an anxiety disorder that may have an element of depression. It helps improve the patient's mental health by modulating the levels of serotonin in the brain.
Used in Treatment of Depression:
Clomipramine hydrochloride is used as an antidepressant for the treatment of depression. It helps to increase the levels of serotonin and norepinephrine in the brain, which are neurotransmitters responsible for regulating mood, thus providing relief from depressive symptoms.
Originator
Anafranil,Ciba Geigy,Switz.,1968
Manufacturing Process
22.9 parts of 3-chloroiminodibenzyl are dissolved in 300 parts by volume of
xylene, and 4 parts of sodium amide, pulverized and suspended in toluene,are added thereto while stirring and maintaining the whole under a nitrogen
atmosphere. The xylene solution immediately turns dark colored, but upon
crystallization of the sodium salt therefrom it becomes again light-colored. The
reaction mixture is stirred for about 2 hours at 80°C until the development of
ammonia has terminated. A solution of γ-dimethylaminopropyl chloride in
toluene, prepared by setting free a corresponding amount of the free base
from 17.4 parts of its hydrochloride salt by addition of aqueous sodium
hydroxide solution in about 10% excess, extraction with toluene and drying
for 2 hours over anhydrous sodium sulfate is added to the xylene solution
containing the sodium salt mentioned above and the whole is stirred under
reflux for 15 hours. Precipitated sodium chloride is filtered off and the filtrate
is concentrated. The residue is diluted with ether, and the hydrochloride of 3-
chloro-5-(γ-dimethylaminopropyl)-iminodibenzyl is precipitated by introducing
dry, gaseous hydrogen chloride. It is filtered off under suction and purified by
repeated recrystallization from acetone; the pure substance melts at 191.5°C
to 192°C.
Therapeutic Function
Antidepressant
Biological Activity
Potent, selective 5-HT uptake blocker. Antidepressant. Binds to the human 5-HT transporter with a K i of 0.05 nmol/l. Also available as part of the Serotonin Uptake Inhibitor Tocriset? .
Clinical Use
#N/A
Veterinary Drugs and Treatments
In veterinary medicine, clomipramine is used primarily in dogs as
a treatment for obsessive-compulsive disorders (ritualistic stereotypical
behaviors) and may be useful for dominance
aggression and
anxiety (separation).
Clomipramine may also be useful in cats, particularly for behaviors
such as urine spraying. One prospective, double-blinded
controlled study in cats with psychogenic alopecia comparing clomipramine
(0.5 mg/kg PO daily) versus placebo showed no statistic
differences in study parameters (Mertens, Torres et al. 2006).
Drug interactions
Potentially hazardous interactions with other drugs
Alcohol: increased sedative effect.
Analgesics: increased risk of CNS toxicity with
tramadol; possibly increased risk of side effects with
nefopam; possibly increased sedative effects with
opioids.
Anti-arrhythmics: increased risk of ventricular
arrhythmias with amiodarone - avoid; increased
risk of ventricular arrhythmias with disopyramide,
flecainide or propafenone; avoid with dronedarone.
Antibacterials: increased risk of ventricular
arrhythmias with delamanid and moxifloxacin and
possibly telithromycin - avoid with delamanid and
moxifloxacin.
Anticoagulants: may alter anticoagulant effect of
coumarins.
Antidepressants: possibly increased serotonergic
effects with duloxetine; enhanced CNS excitation
and hypertension with MAOIs and moclobemide;
concentration possibly increased with SSRIs; risk
of ventricular arrhythmias with citalopram and
escitalopram - avoid; possible increased risk of
convulsions with vortioxetine.
Antiepileptics: convulsive threshold lowered;
concentration reduced by carbamazepine,
phenobarbital and possibly fosphenytoin, phenytoin
and primidone.
Antimalarials: avoid with artemether/lumefantrine
and piperaquine with artenimol.
Antipsychotics: increased risk of ventricular
arrhythmias especially with droperidol, fluphenazine,
haloperidol, pimozide, sulpiride and zuclopenthixol
- avoid; increased risk of ventricular arrhythmias
with risperidone; increased antimuscarinic effects
with clozapine and phenothiazines; concentration
increased by antipsychotics.Antivirals: increased risk of ventricular arrhythmias
with saquinavir - avoid; concentration possibly
increased with ritonavir.
Atomoxetine: increased risk of ventricular
arrhythmias and possibly convulsions.
Beta-blockers: increased risk of ventricular
arrhythmias with sotalol.
Clonidine: tricyclics antagonise hypotensive
effect; increased risk of hypertension on clonidine
withdrawal.
Cytotoxics: increased risk of ventricular arrhythmias
with arsenic trioxide.
Dapoxetine: possibly increased risk of serotonergic
effects - avoid.
Dopaminergics: avoid use with entacapone; CNS
toxicity reported with selegiline and rasagiline.
Methylthioninium: risk of CNS toxicity - avoid if
possible.
Metabolism
Clomipramine is extensively demethylated during
first-pass metabolism in the liver to its primary active
metabolite, desmethylclomipramine. Clomipramine has
been estimated to have a plasma elimination half-life of
about 21 hours; that of desmethylclomipramine is longer
(about 36 hours).Paths of metabolism of both clomipramine and
desmethylclomipramine include hydroxylation and
N-oxidation. About two-thirds of a single dose of
clomipramine is excreted in the urine, mainly in the form
of its metabolites, either free or in conjugated form; the
remainder of the dose appears in the faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 17321-77-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,7,3,2 and 1 respectively; the second part has 2 digits, 7 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 17321-77:
(7*1)+(6*7)+(5*3)+(4*2)+(3*1)+(2*7)+(1*7)=96
96 % 10 = 6
So 17321-77-6 is a valid CAS Registry Number.
InChI:InChI=1/C19H23ClN2.ClH/c1-21(2)12-5-13-22-18-7-4-3-6-15(18)8-9-16-10-11-17(20)14-19(16)22;/h3-4,6-7,10-11,14H,5,8-9,12-13H2,1-2H3;1H
17321-77-6Relevant articles and documents
Crystal form and preparation method of clomipamine hydrochloride
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Paragraph 0027; 0034-0039, (2021/03/11)
The invention belongs to the technical field of medicine crystal forms, and particularly relates to a clomipamine hydrochloride crystal form and a preparation method, and the melting point of clomipamine hydrochloride is 185.1-188.6 DEG C, in an X-ray diffraction pattern scanned by CuK alpha radiation and 2theta (degrees, +/-0.2), diffraction peaks exist at 5.70 degrees, 17.17 degrees, 19.77 degrees and 22.98 degrees, the relative abundance exceeds 50%, diffraction peaks exist at the positions of 20.21 degrees and 28.83 degrees, the relative abundance is 30%-50%, the clomipamine hydrochloridehas diffraction peaks at 23.67 degrees, 24.68 degrees and 29.99 degrees, the relative abundance is 10%-20%, the purity of the clomipamine hydrochloride is high and reaches 99.9%, the single maximum impurity content is 0.02%, and the stability is good.
Efficient synthesis of tertiary amine by direct N-alkylation of secondary amine with carboxylic acid using Ni (0) encat catalyst
Quadri, Syed Aziz Imam,Das, Tonmoy C.,Jadhav, Shivaji,Farooqui, Mazahar
supporting information, p. 267 - 277 (2018/01/08)
In this article, direct N-alkylation of secondary amines with carboxylic acid is described. Readily available diversified carboxylic acid has been explored on variant secondary amines using encapsulated Nickel as catalyst and inexpensive sodium borohydrid
