The discovery of the first antipsychotic in the early 1950s, chlorpromazine, was a great revolution in the treatment of psychoses, especially schizophrenia.

In this article we will talk about a family of antipsychotics: butyrophenones . Within it we find haloperidol (especially known for its usefulness in schizophrenia) and droperidol.

History: the first antipsychotic

The start of research into butyrophenones begins with chlorpromazine.

Chlorpromazine was synthesized as an antihistamine by the French pharmaceutical industry and in 1950, Henri Laborit, a French surgeon, highlighted its sedative effect on psychotic patients. Two years later, in 1952, Delay, Deniker and Harl tested it at the Sainte Anne Hospital in Paris and confirmed its usefulness for the positive psychotic symptoms of schizophrenia .

Since the introduction of the first typical antipsychotic, research on neuroleptics has focused on increasing their efficacy in schizophrenia, reducing the negative symptoms of the disorder and defining their mechanism of action.

Typical and atypical antipsychotics

Typical or first-generation antipsychotics have more side effects than second-generation or atypical ones. The latter appeared with the discovery of Clozapine in the 1970s, which was first marketed in Switzerland and Austria.

Currently there are already second generation or atypical antipsychotics , which also act on the negative symptoms of schizophrenia (which the first generation did not), in addition to the positive symptoms.

Their antipsychotic efficacy is similar to the typical ones, and they differ from them in having a lower incidence of SEP (Extrapyramidal Syndrome: set of motor symptoms) and hyperprolactinemia. (side or adverse effects).

Butyrophenones

Butyrophenones are a family of atypical antipsychotics. Antipsychotics are a type of medication or drugs used to treat schizophrenia and other psychotic disorders, as well as bipolar disorder, among others.

In general, antipsychotics reduce dopamine (DA), an abnormally high brain neurotransmitter in psychotic disorders.

Droperidol

One of the butyrophenone-type antipsychotics is Droperidol, which has a very brief and strongly sedative and tranquilizing action .

Droperidol has a high antiemetic activity (prevents vomiting and nausea). It acts as a dopamine receptor antagonist, being partially selective for D2 receptors.

Its antiemetic action is produced by the antagonism of the AD receptors in a very specific area of the vagus nerve. It is especially useful for the prevention and treatment of postoperative nausea and vomiting and/or induced by opioid analgesics.

It also shows weak antagonistic activity of cholinergic (acetylcholine) muscarinic receptors. Acetylcholine is a neurotransmitter involved in the transmission of nerve impulses and movement.

Features

Droperidol is used for the prevention and treatment of postoperative nausea and vomiting in adults, and second line, in children and adolescents. Also for morphine-induced nausea and vomiting.

As for the route of administration of this type of butyrophenone, this is done through the intravenous route.

Some of its contraindications are: cases of hypersensitivity to the drug or allergy to butyrophenones, bradykinesia (lowering of normal heart rate) and Parkinson’s disease.

Precautions

It should be noted that it is a drug that can increase CNS depression caused by other depressant drugs. In addition, caution should be taken in cases of epilepsy, hypotension, cardiac arrhythmias and chronic alcoholism , among others. The appearance of unexplained fever may be a symptom of neuroleptic malignant syndrome.

The dose in the elderly should be reduced, as well as in those subjects with renal and/or hepatic insufficiency. In patients with breast cancer or prolactin-dependent tumors, it may raise levels of this hormone.

Haloperidol: another type of butyrophenone

Another butyrophenone-type neuroleptic is Haloperidol.

It acts just like the one above, so it is also a potent antagonist to the brain’s dopamine receptors. It is classified among the high-powered neuroleptics . It does not have antihistamine or anticholinergic activity (therefore, it has no side effects of these two types).

The therapeutic indications of haloperidol are diverse. As a neuroleptic it is used in:

  • Delusions and hallucinations (schizophrenia, Korsakoff’s syndrome…)
  • Personality disorder: paranoid, schizoid, schizotypal, borderline…

As a treatment for psychomotor agitation, some of its uses are for:

  • Mania, dementia, intellectual disability, alcoholism.
  • Personality disorders.
  • Agitation, aggressiveness .
  • Behavioral disorders.
  • Tics, stuttering, Tourette’s Syndrome symptoms…

Like Droperidol, as an antiemetic it prevents vomiting and nausea of various aetiologies.

It is contraindicated in cases of hypersensitivity to medication, coma, central nervous system depression from alcohol or other depressants, Parkinson’s disease and basal ganglia injury.

Bibliographic references:

  • Ortiz, A., De la Mata, I. (2001). New antipsychotics, 25(1), 1-8. National Health System.
  • General Council of Official Associations of Pharmacists. (2012). Catalogue of Medicines. Consejo Collection.
  • Inchauspe, J.A. and Valverde, M.A. (2018). Believing in Clozapine: Faith and Evidence. Rev. Neuropsiq, 38(133), 239-262.