Etoperidone: uses, characteristics and side effects

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

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

• Related article: "Types of antidepressants: characteristics and effects"

What is etoperidone and what effects does it produce?

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

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

Although etoperidone has certain sedative effects, it differs from other minor tranquilizers in some fundamental aspects: in its interaction with the main cerebral amines; by the absence of anticonvulsant effects; and in its different spectrum of effects at the behavioral level when consumed in high doses.

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

How does this drug work?

Ethoperidone acts as a drug that antagonizes several receptors, including those for 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 the monoamine transporters: serotonin, norepinephrine, and dopamine. The administration of this type of antidepressants in the acute phase increases, mainly, the availability of noradrenaline and, to some extent, that of 5-HT, by blocking its reuptake into the synaptic cleft.

Prolonged use negatively regulates alpha-adrenergic receptors in the postsynaptic membrane, a possible final common pathway of the antidepressant activity of these drugs.

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

• You may be interested in: "Types of psychoactive drugs: uses and side effects"

Second-generation tricyclic or atypical antidepressants

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

Tricyclic antidepressants have been used for decades and have some chemical and, to a lesser extent, pharmacological similarity to the phenothiazines, used to treat serious mental and emotional disorders. Although initially it was thought that this type of antidepressants were useful as antihistamines, over time their use was limited to the treatment of depression and other similar pathologies.

These types of antidepressants are highly effective., although due to the number of side effects they produce, it is usually recommended to start treatment with a low dose and gradually increase it depending on the tolerance that each patient has and the antidepressant effect that is achieved, until finding a balance between the greatest possible efficacy and the least amount of effects secondary.

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

Currently, this type of antidepressant they have been replaced by new generation ones, with fewer side effects and a more specific and selective mechanism of action, such as venlafaxine or mirtazapine, two serotonin and norepinephrine reuptake inhibitors.

Side effects

The most common side effects When drugs from the group of atypical or heterocyclic antidepressants, such as etoperidone, are consumed, they include a whole series of effects at the somatic level, such as the following:

• Nausea
• Fatigue
• Nervousness
• dry mouth
• dizziness
• Diarrhea
• Headaches
• Insomnia

contraindications

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

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

Specific contraindications to the use of etoperidone include the following:

• Allergy to etoperidone, trazodone, or other phenylpiperazines.
• Bipolar disorders and manic states: This drug can accelerate the transition to the hypomanic or manic phase and induce a rapid and reversible cycle between mania and depression.
• Cardiovascular disorders: 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: due to the fact that it is mainly metabolized in the liver, the dosage must be adjusted to the hepatic functional level of each patient.
• Renal insufficiency: since the drug is mainly eliminated via the kidneys, the dosage should be adjusted according to the renal functional level.

Bibliographic references:

• Heerlein A. Antidepressants. In: Heerlein A (ed): Clinical Psychiatry. Santiago de Chile, Editions of the Society of Neurology, Psychiatry and Neurosurgery, 2000
• Raffa, RB; Shank, R. P.; 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 norepinephrine reuptake inhibitors compared to classic 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