Etoperidone: uses, characteristics and side effects

This type of tricyclic antidepressant is less and less used, due to its side effects.

Etoperidone is an atypical antidepressant, or second-generation tricyclic antidepressant.or second generation tricyclic, used to treat depressive disorders and which was developed decades ago, although it is now discontinued. At present, other new generation antidepressants are used, which have fewer side effects than those of the drugs of this family.

In this article we explain what etoperidone is and what effects it produces, what is its mechanism of action and that of tricyclic antidepressants, what side effects it causes and what are the main contraindications if you are going to use this drug.

What is etoperidone and what effects does it produce?

Etoperidone is a drug of the atypical antidepressant group (second generation tricyclic) that was developed in the 1970s by the Italian pharmaceutical company Angelini and is no longer marketed.

It belongs to the phenylpiperazine group.It has a chemical structure similar to other drugs such as trazodone and nefazodone, both of which are also second-generation antidepressants that act as serotonin reuptake antagonists and inhibitors, with anxiolytic and hypnotic effects.

Although etoperidone has certain sedative effects, it differs from the rest of the minor tranquilizers in some fundamental aspects: in its interaction with the main brain amines; in the absence of Anticonvulsant effects; and in its different spectrum of behavioral effects when consumed in high doses.

Etoperidone, however, is similar in some respects to neuroleptic drugs (drugs used to treat psychosis and extreme agitation), such as chlorpromazine. (drugs used to treat psychosis and states of extreme agitation), such as chlorpromazine, in that it produces analgesic and sedative effects at low doses; however, unlike the latter, it does not block dopaminergic receptors at the central level.

How does this drug work?

Etoperidone acts as an antagonist drug of several receptors, including serotonin and adrenergic receptors.. It also appears to have a mild affinity for blocking dopamine, histamine and acetylcholine (muscarinic-type) receptors.

In addition to blocking these receptors, this drug also has a weak affinity for monoamine transporters: serotonin, noradrenaline and dopamine. The administration of this type of antidepressant in the acute phase mainly increases the availability of noradrenaline and, to some extent, that of 5-HT, by blocking its reuptake into the synaptic cleft.

Prolonged use negatively upregulates alpha-adrenergic receptors on the postsynaptic membranea possible common final pathway of the antidepressant activity of these drugs.

On the other hand, in its metabolization, etoperidone produces an active substance or metabolite called mCPP, probably responsible for the serotonergic effects; a substance that can cause undesirable and unpleasant effects in subjects who consume or have consumed this antidepressant.

Atypical antidepressants or second-generation tricyclics

Etoperidone belongs to the group of atypical or tricyclic antidepressants, frequently used in patients suffering from major depression and responding inadequately or enduring intolerable side effects during first-line treatment with serotonin reuptake inhibitor antidepressants.

Tricyclic antidepressants have been used for decades and have some chemical and, to a lesser extent, chemical similarity. have some chemical and, to a lesser extent, pharmacological similarity to phenothiazinesused to treat severe mental and emotional disorders. Although these types of antidepressants were initially thought to be useful as antihistamines, over time their use was limited to the treatment of depression and other similar pathologies.

This type of antidepressant has a high efficacy.However, due to the number of side effects they produce, it is usually recommended to start treatment with a low dose and increase it according to the tolerance of each patient and the antidepressant effect achieved, until a balance is found between the highest possible efficacy and the lowest number of side effects.

Given their sedative profile, this type of drug can also be used to treat patients with depression. to treat depressed patients with a high level of anxiety, helping them to calm down the depression.They can also be used to treat depressed patients with a high level of anxiety, helping them to calm the nervousness and agitation that they usually present in certain circumstances.

At present, this type of antidepressants have been replaced by other have been replaced by others of a new generation, with fewer side effects and a more specific mechanism of action. and a more specific and selective mechanism of action, such as venlafaxine or mirtazapine, two serotonin and noradrenaline reuptake inhibitors.

Side effects

The most common side effects when taking drugs of the atypical or heterocyclic antidepressant group, such as etoperidone, include a series of somatic effects, such as the following:

• Nausea
• Fatigue
• Nervousness
• Dry mouth
• Dizziness
• Diarrhea
• Headaches
• Insomnia

Contraindications

Although these types of antidepressant drugs were effective in their day and when they were developed, they are nowadays less and less used, since their overdose is toxic and they have more adverse effects than more modern antidepressants.. These side effects are mainly due to muscarinic and histaminic blockades and alpha-adrenergic actions.

Many of the atypical antidepressants have potent anticholinergic properties and are therefore not suitable for the elderly or for patients suffering from benign prostatic hypertrophy, glaucoma or chronic constipation. In addition, the vast majority of drugs of this type are not suitable for the elderly, the vast majority of drugs of this type lower the seizure threshold, with the consequent danger for people prone to seizures. for people prone to seizures.

Specific contraindications to the use of ethoperidone include the following:

• Allergy to ethoperidone, trazodone or other phenylpiperazines.
• Bipolar disturbances and manic states: this drug may accelerate the transition to the hypomanic or manic phase and induce a rapid and reversible cycle between mania and depression.
• Cardiovascular disorders: it increases the risk of arrhythmias, congestive heart failure, myocardial infarction or cardiovascular accident.
• Schizophrenia and psychosis: may increase the risk of psychotic disturbances.
• Hyperthyroidism: due to the risk of cardiovascular toxicity.
• Hepatic insufficiency: since it is mainly metabolized in the liver, the dosage should be adjusted to the hepatic functional level of each patient.
• Renal insufficiency: since the drug is mostly eliminated via the kidneys, the dosage should be adjusted according to the renal functional level.

Bibliographic references:

• Heerlein A. Antidepressants. In: Heerlein A (ed): Psiquiatría Clínica. Santiago de Chile, Ediciones de la Sociedad de Neurología, Psiquiatría y Neurocirugía, 2000.
• Raffa, RB; Shank, RP; Vaught, JL (1992). "Etoperidone, trazodone and MCPP: in vitro and in vivo identification of serotonin 5-HT1A (antagonistic) activity". Psychopharmacology. 108(3): 320-6
• Rodriguez, N. H. (2015). Effectiveness of atypical antidepressants and serotonin and noradrenaline reuptake inhibitors versus classical serotonin reuptake inhibitors. PHARMACIENCIA, 3(1), 39-42.
• Tordera RM, Monge A, Del Rio J, Lasheras B. Antidepressant-like activity of VN2222, a serotonin reuptake inhibitor with high affinity at 5-HT(1A) receptors. Eur J Pharmacol 2002; 442(1-2):63-71.