Tofranil (Imipramine) is an antidepressant used for the treatment of major depression and functional enuresis in children (bedwetting). Although it has been associated with relieving depression, it has also been successfully used to alleviate suicidal tendencies. Chemically it belongs to the dibenzazepine family.
Imipramine, the active drug in Tofranil, was developed in the 1950s. It was the first drug in the tricyclic antidepressant (TCA) family. Imipramine made two fundamental contributions to the development of psychiatry: one was the dramatic change it brought to the psychiatric care of those experiencing depression, and the other of a purely pharmacological nature, permitting, among other things, the development of a hypotheses of depressive disorders.
The mechanism of action of this medication is similar to that of other tricyclic antidepressants. Its antidepressant activity is thought to relate primarily to its inhibition of serotonin and norepinephrine reuptake. Tofranil has more serotonin effects initially; its metabolite, Norpramin, then balances this effect with more norepinephrine transport inhibition. On the other hand, Tofranil is highly anticholinergic and is a relatively effective serotonin reuptake inhibitor. It also has moderate activity for alpha-1 adrenoreceptors and Histamine-1 receptors.
This drug is a dibenzazepine derivative of tricyclic antidepressants. It is off-white in color and crystalline in nature. It is available as a hydrochloride. It is odorless and has a pKa value of 9.5. On exposure to light, Tofranil turns yellow and can result in the loss of potency. It is stable in a pH range of 4–5.
The primary and most common adverse effects of TCAs are the anticholinergic effects. These include:
Since this medication is a tertiary amine, these effects are more severe than with the secondary amine tricyclic antidepressants, such as Norpramin. Tofranil is also a potential blocker of the alpha receptors, thus it also produces orthostatic hypotension—the medical term for the dizzy feeling you get when you stand up too quickly. It can also cause weight gain, sedation, and changes in heart rate.
This drug, like other TCAs, has several important drug interactions of which to be aware. If you are prescribed this medication, ensure that your pharmacist and/or doctor shares the following drug interaction safety information:
Alcohol: Alcohol increases the sedative effects of this medication.
Monoamine Oxidase Inhibitors (MAOIs): Treatment with this medication should not be started until two weeks after stopping treatment with MAOIs. Conversely, MAOIs should not be started until one to two weeks after stopping Tofranil.
Antiepileptic agents: This medication decreases the antiepileptic effects of such medications.
Antihistamine: There is an increase in the sedative effects due to the increased muscarinic effects when both drugs are administered together.
Anxiolytics and hypnotics: There is an increase in sedative effects during concurrent administration.
Barbiturates: This medication antagonizes the anticonvulsant effects of barbiturates.
Nitrates: The effect of nitrates is decreased when administered with this medication because of the dry mouth side effect of Tofranil.
Antihypertensive: Hypotensive effects are increased when mixed with this drug.
Sibutramine: Tofranil and sibutramine combined severely increase the risk of developing serotonin syndrome, which is a potentially fatal condition.
Although this drug is not classified as addictive, stopping treatment with it abruptly may cause uncomfortable withdrawal symptoms including nausea, headache, fatigue, and general malaise. If you need to stop taking this medication, work out a safe plan with your doctor to taper off your dosage gradually. This will go a long way toward reducing the severity and occurrence of withdrawal symptoms.
Page content reviewed by James Pendleton, ND
Last Update: 04-22-2015
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