Pertofran

Pertofran - General Information

A tricyclic dibenzazepine compound that potentiates neurotransmission. Pertofran selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. [PubChem]

Pharmacology of Pertofran

Pertofran, a tertiary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. Pertofran is used to treat depression, pain of neuropathic origin, attention_deficit hyperactivity disorder, functional enuresis in children, panic and phobic disorder, and to manage some eating disorders. Pertofran inhibits the re-uptake of noradrenaline at the noradrenergic nerve endings and the re-uptake of serotonin (5-hydroxy tryptamine) at the serotoninergic nerve endings in the central nervous system. These two effects are considered to be the likely base of the antidepressant effect of Pertofran. The drug also has a strong anticholinergic effect and serves as an antagonist on a1 and H1 receptors.

Pertofran for patients

Pertofran Interactions

1. Drugs Metabolized by P450 2D6: The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7 to 10% of caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the traction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8 fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble p.o. metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythrnics propatenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, seriraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of T. A. with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

2. Close supervision and careful adjustment of dosage are required when this drug is given concomitantly with anticholinergic or sympathomimetic drugs.

3. Clinical experience in the concurrent administration of ECT and antidepressant drugs is limited. Thus, if such treatment is essential, the possibility of increased risk relative to benefits should be considered.

4. If desipramine hydrochloride is to be combined with other psychotropic agents such as tranquilizers or sedative/hypnotics, careful consideration should be given to the pharmacology of the agents employed since the sedative effects of desipramine and benzodiazepines (e.g., chlordiazepoxide or diazepam) are additive. Both the sedative and anticholinergic effects of the major tranquilizers are also additive to those of desipramine.

5. Concurrent administration of cimetidine and tricyclic antidepressants can produce clinically significant increases in the plasma levels of the tricyclic antidepressants. Conversely, decreases in plasma levels of the tricyclic antidepressants have been reported upon discontinuation of cimetidine which may result in the loss of the therapeutic efficacy of the tricyclic antidepressant

6. There have been greater than two-fold increases of previously stable plasma levels of tricyclic antidepressants when fluoxetine has been administered in combination with these agents.

Pertofran Contraindications

Desipramine hydrochloride should not be given in conjunction with, or within 2 weeks of, treatment with an MAO inhibitor drug; hyperpyretic crises, severe convulsions, and death have occurred in patients taking MAO inhibitors and tricyclic antidepressants. When desipramine hydrochloride is substituted for an MAO inhibitor, at least 2 weeks should elapse between treatments. Desipramine hydrochloride should then be started cautiously and should be increased gradually.

The drug is contraindicated in the acute recovery period following myocardial infarction. It should not be used in those who have shown prior hypersensitivity to the drug. Cross sensitivity between this and other dibenzazepines is a possibility.

Additional information about Pertofran

Pertofran Indication: For relief of symptoms in various depressive syndromes, especially endogenous depression.
Mechanism Of Action: Pertofran is a tricyclic antidepressant that selectively blocks reuptake of norepinephrine (noradrenaline) from the neural synapse. It also appears to impair serotonin transport. Pertofran also possesses minor anticholinergic activity, through its affinity to muscarinic receptors. Evidence also suggests that Desiprmaine binds to and down regulates histamine and beta adrenergic receptors. Tricyclic drugs are believed to act by restoring normal levels of neurotransmitters by blocking the re-uptake of these substances from the synapse in the central nervous system.
Drug Interactions: Altretamine Risk of severe hypotension
Atazanavir Atazanavir increases the effect and toxicity of tricyclics
Carbamazepine The tricyclic increases the effect of carbamazepine
Cimetidine Cimetidine increases the effect of tricyclic agent
Cisapride Increased risk of cardiotoxicity and arrhythmias
Clonidine The tricyclic decreases the effect of clonidine
Dihydroquinidine barbiturate Quinidine increases the effect of tricyclic agent
Dobutamine The tricyclic increases the sympathomimetic effect
Donepezil Possible antagonism of action
Dopamine The tricyclic increases the sympathomimetic effect
Duloxetine Possible increase in the levels of this agent when used with duloxetine
Ephedra The tricyclic increases the sympathomimetic effect
Ephedrine The tricyclic increases the sympathomimetic effect
Epinephrine The tricyclic increases the sympathomimetic effect
Fenoterol The tricyclic increases the sympathomimetic effect
Fluoxetine Fluoxetine increases the effect and toxicity of tricyclics
Fluvoxamine Fluvoxamine increases the effect and toxicity of tricyclics
Galantamine Possible antagonism of action
Grepafloxacin Increased risk of cardiotoxicity and arrhythmias
Guanethidine The tricyclic decreases the effect of guanethidine
Isocarboxazid Possibility of severe adverse effects
Isoproterenol The tricyclic increases the sympathomimetic effect
Mephentermine The tricyclic increases the sympathomimetic effect
Metaraminol The tricyclic increases the sympathomimetic effect
Methoxamine The tricyclic increases the sympathomimetic effect
Moclobemide Possible severe adverse reaction with this combination
Norepinephrine The tricyclic increases the sympathomimetic effect
Orciprenaline The tricyclic increases the sympathomimetic effect
Phenelzine Possibility of severe adverse effects
Phenylephrine The tricyclic increases the sympathomimetic effect
Phenylpropanolamine The tricyclic increases the sympathomimetic effect
Pirbuterol The tricyclic increases the sympathomimetic effect
Procaterol The tricyclic increases the sympathomimetic effect
Pseudoephedrine The tricyclic increases the sympathomimetic effect
Quinidine Quinidine increases the effect of tricyclic agent
Quinidine barbiturate Quinidine increases the effect of tricyclic agent
Rasagiline Possibility of severe adverse effects
Rifabutin The rifamycin decreases the effect of tricyclics
Rifampin The rifamycin decreases the effect of tricyclics
Ritonavir Ritonavir increases the effect and toxicity of tricyclics
Rivastigmine Possible antagonism of action
Salbutamol The tricyclic increases the sympathomimetic effect
Sibutramine Increased risk of CNS adverse effects
Sparfloxacin Increased risk of cardiotoxicity and arrhythmias
Terbinafine Terbinafine increases the effect and toxicity of the tricyclic
Terbutaline The tricyclic increases the sympathomimetic effect
Terfenadine Increased risk of cardiotoxicity and arrhythmias
Tranylcypromine Possibility of severe adverse effects
Food Interactions: Avoid alcohol.
Take with food to reduce irritation, limit caffeine intake.
Generic Name: Desipramine
Synonyms: DMI; Demethylimipramine; Desimipramine; Desimpramine; Desipramin; Desipramine Hcl; Desmethylimipramine; Dezipramine; Dimethylimipramine; Methylaminopropyliminodibenzyl; Monodemethylimipramine; Norimipramine; Norpramine
Drug Category: Antidepressants; Norepinephrine-Reuptake Inhibitors
Drug Type: Small Molecule; Approved

Other Brand Names containing Desipramine: Pentofran; Pertofran; Pertrofane; Sertofran;
Absorption: Desipramine hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. 90.5% (range 73-92%) of desipramine binds to plasma proteins.
Toxicity (Overdose): Male mice: LD₅₀ = 290 mg/kg, female rats: LD₅₀ = 320 mg/kg
Protein Binding: 15%
Biotransformation: Desipramine is extensively metabolized in the liver and is cleared mainly by 2-hydroxylation and glucuronidation, whereas 10-hydroxylation is of minor importance. The 2-hydroxylation metabolic pathway of desipramine is under genetic control.
Half Life: 21-23 hours
Dosage Forms of Pertofran: Tablet Oral
Chemical IUPAC Name: 3-(5,6-dihydrobenzo[b][1]benzazepin-11-yl)-N-methylpropan-1-amine
Chemical Formula: C18H22N2
Desipramine on Wikipedia: https://en.wikipedia.org/wiki/Desipramine
Organisms Affected: Humans and other mammals