Butyrophenone is a pharmacological agent that is the basic substance for a whole group of drugs called butyrophenones. Among other things, butyrophenones serve as antipsychotics for the treatment of schizophrenia and mania. In this context, they act as antagonists of the neurotransmitter dopamine.
What is butyrophenone?
Butyrophenones serve as antipsychotics for the treatment of schizophrenia and mania, among other conditions. Butyrophenone represents the lead compound for a whole range of agents known as butyrophenones. All butyrophenones have the same basic chemical structure. According to chemical nomenclature, the exact name for butyrophenone is 1-phenylbutan-1-one. Butyrophenones are mainly used as neuroleptics (antipsychotics). Among these neuroleptics, there are high-potency agents as well as intermediate- and low-potency agents. Simply belonging to the butyrophenone group says nothing about the strength of the compounds’ efficacy. High-potency butyrophenones include haloperidol, benperidol, trifluperidol, and bromperidol. Other compounds, such as droperidol, melperone, and pipamperone, have moderate or weak potency. Some butyrophenones have antiemetic activity in addition to antipsychotic activity. As antiemetics, these drugs can also suppress nausea and emesis, among other symptoms. Since the mid-fifties, butyrophenones have been used initially for research purposes and since the early sixties for clinical use in psychiatry.
Pharmacological action
The mode of action of butyrophenones is based on their strong affinity for dopamine receptors. When used, they compete with dopamine for the appropriate receptors. The result is inhibition of dopamine action. Dopamine is a versatile neurotransmitter, which is particularly known for its uplifting effect. Therefore, it is also popularly known as the happiness hormone. Its main function is to motivate and increase drive. However, if too much dopamine is released, psychotic symptoms occur, which can be attributed to the disease complex of schizophrenia. Thus, four different pathways of action of dopamine are known in the organism. These include the mesolimbic system, the mesostriatal system, the mesocortical system, and the tuberoinfundibular system. The mesolimbic system is also known as the positive reward system because it is instrumental in the generation of positive emotions such as pleasure. However, overactivity in this area produces the positive symptoms of schizophrenia, which are associated with exaggerations and misinterpretations of perceptions. Meanwhile, the mesostriatal system plays an important role in movement control and, when underactive, produces the symptoms of Parkinson’s disease due to insufficient dopamine activity. The mesocortical system controls the so-called executive functions, which are expressed in the higher mental and cognitive processes. Finally, the tuberoinfundibular system is responsible for the release of prolactin. In the context of blocking dopamine action by butyrophenones, all these processes are affected simultaneously. Thus, overactivity of dopamine can be attenuated, but at the same time, the reduced dopamine action in certain areas of the system leads to undesirable side effects.
Medical application and use
All agents in the butyrophenone drug class are antagonists of the neurotransmitter dopamine and are used to treat dopamine overactivity. Because overactivity of dopamine in the mesolimbic system leads to the positive symptoms of schizophrenia, the use of butyrophenones as psychotropic drugs to alleviate symptoms occurs in these cases. At the same time, some butyrophenones also show a good effect against nausea and vomiting. However, the effect of the individual active ingredients varies. This depends, among other things, on their affinity for dopamine receptors. Haloperidol and benperidol, for example, are among the highly effective antipsychotics. With haloperidol, a sedative effect initially occurs after treatment. Only after a few days does the actual antipsychotic effect occur. The drug is therefore often used in the acute phases of schizophrenia and in mania.Benperidol, on the other hand, is now only considered a reserve drug, since in addition to the desired antipsychotic effects, side effects in the form of Parkinson’s-like symptoms are increasingly occurring. Droperidol has a great influence on the vomiting center of the brain and is mainly used for nausea and vomiting felt after operations. However, it also shows many side effects and should not be used in a variety of conditions, including Parkinson’s disease, depression, too low a pulse, or comatose states. Melperone is used as a medium- or low-potency neuroleptic in elderly patients to treat confusion, tension or sleep disorders. Pipamperone has a mainly sedative effect without a major antipsychotic effect. It is mainly used in sleep disorders, internal agitation states or increased aggressiveness. Therefore, it is also frequently used in child and adolescent psychiatry.
Risks and side effects
Butyrophenones can also produce significant side effects, depending on their potency. While low-potency butyrophenones usually produce only mild side effects, high-potency butyrophenones often exhibit unpleasant side effects. These manifest themselves in involuntary movements. The patient is restless and can no longer control his repetitive movements. The side effects go in the direction of Parkinson’s-like movement disorders. Depression, seizures, hormonal disturbances, blood formation disorders and headaches are also sometimes observed. A particularly dramatic complication is the so-called malignant neuroleptic syndrome, which can be fatal in extreme cases. In this syndrome, massive motor, vegetative and psychological symptoms occur. Although this side effect is very rare, the syndrome can be caused by the use of any butyrophenone if a certain risk potential is present. In this case, the most important measure is the immediate discontinuation of the corresponding drug.
