Imipramine | Tricyclic Antidepressant | CAS 50-49-7

Product Name: Imipramine
CAS No.: 50-49-7 (base)
Chemical Name: N,N-dimethyl-10,11-dihydro-5H-dibenz[b,f]azepine-5-propanamine
Molecular Formula: C₁₉H₂₄N₂
Appearance: White or slightly yellowish crystalline powder
Solubility: Imipramine hydrochloride is freely soluble in water and ethanol
Stability: Relatively stable but sensitive to light
Common salt: Hydrochloride

1. Introduction

Imipramine is a tricyclic antidepressant (TCA), one of the first drugs in this group. It inhibits norepinephrine and serotonin reuptake, increasing their concentration in the synaptic cleft. It is used for the treatment of depression, panic disorders, and nocturnal enuresis.

Imipramine, discovered in the 1950s, became the progenitor of the tricyclic antidepressant class and revolutionized the pharmacotherapy of depressive disorders. Its antidepressant effect is associated with the modulation of neurotransmitter systems in the brain, primarily noradrenergic and serotonergic. Despite the emergence of new classes of antidepressants with better tolerability profiles, imipramine retains its importance in the treatment of certain types of depression and other psychiatric disorders.

2. Chemical Structure & Synthesis

The molecule contains a tricyclic dibenzazepine system to which a propylaminodimethyl side chain is attached.

Synthesis: Imipramine is synthesized from iminostilbene (10,11-dihydro-5H-dibenz[b,f]azepine). Iminostilbene is alkylated with 3-dimethylaminopropyl chloride in the presence of sodium amide or another strong base. It is typically used as the hydrochloride salt.

3. Mechanism of Action

The main mechanism of antidepressant action of imipramine is inhibition of norepinephrine and serotonin reuptake from the synaptic cleft into presynaptic neurons. This leads to an increase in the concentration of these monoamines in the synaptic cleft and enhancement of their postsynaptic action. Imipramine also has activity at other receptors:

• M-cholinergic (antimuscarinic) action – causes side effects such as dry mouth, constipation, urinary retention, tachycardia, and accommodation disturbance

• α₁-adrenergic blocking action – may cause orthostatic hypotension and dizziness

• H₁-histamine blocking action – manifests as sedative effects and weight gain

4. Pharmacokinetics

Well absorbed from the gastrointestinal tract. Undergoes intensive first-pass metabolism in the liver, forming the active metabolite desipramine (which primarily inhibits norepinephrine reuptake). High degree of plasma protein binding. Metabolized in the liver by demethylation, hydroxylation, and conjugation. Excreted primarily by the kidneys.

5. Applications

• Depressive disorders of various etiologies and severity, especially with psychomotor retardation

• Panic disorders with or without agoraphobia

• Obsessive-compulsive disorder (OCD) – less effective than SSRIs

• Nocturnal enuresis in children over 6 years of age (in the absence of organic pathology)

• Chronic pain syndromes – e.g., neuropathic pain, migraine (as adjunctive therapy)

6. Conclusion

Imipramine is a classic tricyclic antidepressant with proven efficacy in the treatment of depression and some other psychiatric disorders. Its use requires careful dose selection and monitoring due to its broad spectrum of pharmacological activity and the risk of side effects, especially cardiotoxicity in overdose and anticholinergic reactions. Despite this, imipramine remains an important tool in the arsenal of psychiatrists for the treatment of patients who do not respond to other therapies.