Imipramine works by inhibiting the neuronal reuptake of the neurotransmitters norepinephrine and serotonin. It binds the sodium-dependent serotonin transporter and sodium-dependent norepinephrine transporter reducing the reuptake of norepinephrine and serotonin by neurons. Depression has been linked to a lack of stimulation of the post-synaptic neuron by norepinephrine and serotonin. Slowing the reuptake of these neurotransmitters increases their concentration in the synaptic cleft, producing knock-on effects in protein kinase signaling which is thought to contribute to changes in neurotransmission and brain physiology which relieves symptoms of depression.
Imipramine affects numerous neurotransmitter systems known to be involved in the etiology of depression, anxiety, attention-deficit hyperactivity disorder (ADHD), enuresis and numerous other mental and physical conditions. Imipramine is similar in structure to some muscle relaxants, and has a significant analgesic effect and, thus, is very useful in some pain conditions.
The mechanisms of imipramine’s actions include, but are not limited to, effects on:
Serotonin: very strong reuptake inhibition.
Norepinephrine: strong reuptake inhibition. However, it has less affinity to norepinephrine transporter than desipramine.
Dopamine: imipramine blocks D2 receptors. However, imipramine, and its metabolite, desipramine, have no appreciable affinity for the dopamine transporter.
Acetylcholine: imipramine is an anticholinergic, specifically an antagonist of the muscarinic acetylcholine receptors. Thus, it is prescribed with caution to the elderly and with extreme caution to those with psychosis, as the general brain activity enhancement in combination with the “dementing” effects of anticholinergics increases the potential of imipramine to cause hallucinations, confusion and delirium in this population.
Epinephrine: imipramine antagonizes adrenergic receptors, thus sometimes causing orthostatic hypotension.
Histamine: imipramine is an antagonist of the histamine H1 receptors.
BDNF: BDNF is implicated in neurogenesis in the hippocampus, and studies suggest that depressed patients have decreased levels of BDNF and reduced hippocampal neurogenesis. It is not clear how neurogenesis restores mood, as ablation of hippocampal neurogenesis in murine models do not show anxiety related or depression related behaviours. Chronic imipramine administration results in increased histone acetylation (which is associated with transcriptional activation and decondensed chromatin) at the hippocampal BDNF promotor, and also reduced expression of hippocampal HDAC5.
Storage conditions: Store in cool & dry place, Protect from light
Packaging: : polyethylene nylon plastic bag