Treatment of Psychological Disorders
Mohamed Ahmed Abd El-Hay in Understanding Psychology for Medicine and Nursing, 2019
Chlorpromazine was the first antipsychotic drug, it was administered to psychiatric patients in 1952. Shortly thereafter, two other prototypes of antipsychotics were developed: reserpine (introduced in 1954) and haloperidol (introduced in 1958). Investigations of these three prototype antipsychotics contributed to the formulation of the dopamine hypothesis of schizophrenia and the production of numerous classes of conventional antipsychotics. The various biochemical classes of these drugs were marked by their ability to block D2 receptors. This group of antipsychotics is now called first-generation, conventional, or typical antipsychotics. Typical antipsychotics were marked by their extrapyramidal side effects, their potential to produce tardive dyskinesia, and increased serum prolactin: all result from D2 blockage. The conventional antipsychotic medications are classified according to their chemical structure into the phenothiazines, butyrophenones, thioxanthenes, dihydroindolones, dibenzepines, and diphenylbutylpiperidines. They are considered to be equally effective in the treatment of psychotic symptoms of schizophrenia, but vary in their individual properties, side effects, and potency (Miyamoto, Stroup, Duncan, Aoba, & Lieberman, 2003).
Arvid Carlsson (1923–2018)
Andrew P. Wickens in Key Thinkers in Neuroscience, 2018
During the early part of the 1960s, Carlsson turned his attention towards understanding the pharmacological action of the antipsychotic drugs chlorpromazine and haloperidol, which were then being used extensively to treat schizophrenia. Both these drugs produced side effects similar to reserpine, including sedation and immobility – yet, neither depleted the brain of dopamine. Working with Margit Lindvist, who had first introduced Carlsson to laboratory techniques as a young medical student in 1944, Carlsson discovered that the administration of either chlorpromazine or haloperidol increased the levels of dopamine breakdown product 3-methoxytyramine in the striatum while leaving the dopamine levels unchanged. This was an odd finding – although one that could be explained using a leap of imagination. In short, Carlsson and Lindvist proposed that instead of reducing the stores of dopamine (as reserpine does), chlorpromazine and haloperidol exerted their effects by blocking postsynaptic dopamine receptors. In turn, this blockade led to a feedback signal instructing the presynaptic neurons to release more neurotransmitter. This was a radical idea not only because it advocated receptor blockade but also because it was the first time a receptor-mediated feedback control had been suggested to act in the nervous system. Again, Carlsson would be proven correct over the subsequent years by numerous workers using a variety of different techniques. These observations also formed the basis for the “dopamine hypothesis of schizophrenia”, which saw the illness as resulting from abnormal activity of dopamine systems in the brain. Today, despite its limitations, this still remains the most viable theory of schizophrenia.
Imaging Neuroreceptors to Study Drug Action in Living Human Brain
Edythe D. London in Imaging Drug Action in the Brain, 2017
Drugs generally act by stimulating or blocking receptors. Drugs that block dopamine receptors diminish delusions and hallucinations and improve cognitive function in psychotic patients. Seeman et al. (1976) and Creese et al. (1976) both demonstrated the relationship between the in vitro binding affinity of various dopamine antagonists and their typical clinical daily dose used to treat schizophrenia. Carlsson et al. (1978) among others proposed a dopamine hypothesis for schizophrenia.
More than a Half-Century with Haloperidol: Glories, Disparities, and Use Today
Published in Issues in Mental Health Nursing, 2023
These days, it might be difficult to imagine the initial glory of haloperidol, but it was a sensation in the realms of psychiatry and mental health (Seeman, 2021; Tyler et al., 2017). It is now thought the medication aided in understanding how dopaminergic changes result in the desired effects of antipsychotics, paving the way for many medications to come; haloperidol also probably furthered the biochemistry understanding of psychosis and schizophrenia spectrum disorders, helping kickstart the dopamine hypothesis of schizophrenia (Tyler et al., 2017; Seeman, 2021). Additionally, in the first decades of use, the antipsychotic effects of haloperidol may have offered relief to so many individuals that it was a major player in accelerating deinstitutionalization, which ultimately occurred across the United States (Tyler et al., 2017).
An evaluation of lumateperone tosylate for the treatment of schizophrenia
Published in Expert Opinion on Pharmacotherapy, 2020
Pankhuri Vyas, Brian Jaeho Hwang, James Robert Brašić
The dopamine hypothesis of schizophrenia proposed that positive symptoms of schizophrenia result from dysfunction of dopaminergic neurotransmission [6]. In the resting tonic state, people with schizophrenia may exhibit lower extracellular dopamine than healthy individuals; in the excited phasic state, people with schizophrenia may experience higher intrasynaptic dopamine levels than healthy individuals [7]. The excessive intrasynaptic dopamine may be associated with the positive symptoms of schizophrenia.
A diffusion weighted imaging study of basal ganglia in schizophrenia
Published in International Journal of Psychiatry in Clinical Practice, 2018
Giuseppe Delvecchio, Alessandro Pigoni, Cinzia Perlini, Marco Barillari, Amelia Versace, Mirella Ruggeri, A. Carlo Altamura, Marcella Bellani, Paolo Brambilla
Since the introduction of structural magnetic resonance imaging (MRI), numerous neuroimaging studies provided evidence of selective brain abnormalities in several cortical and subcortical structures in schizophrenia (Zampieri et al. 2014; van Erp et al. 2014, 2016; Zhang et al. 2015; Yue et al. 2016). Among these structures, the basal ganglia deserve particular attention, being subcortical nuclei rich in dopaminergic neurons (Cazorla et al. 2014). They are composed by the caudate nucleus, the lenticular nucleus (which comprises the putamen and the globus pallidus), the subthalamic nucleus and the substantia nigra. The housing of dopaminergic neurons in these structures explained their involvement in the neuropathology of schizophrenia, a well-established dopaminergic disorder (Brisch et al. 2014). Indeed, the classical ‘dopamine hypothesis’ of schizophrenia proposed that hyperactivity of dopamine transmission might be responsible for symptoms in psychosis and schizophrenia (Howes and Kapur 2009). In particular, by inhibiting the dopaminergic signaling of D2-receptors, which are highly concentrated in the basal ganglia, the antipsychotic drugs seem to reduce positive psychotic symptoms in patients affected by schizophrenia and therefore they have been considered the preferential treatment of this disorder (Dunlop and Brandon 2015). Furthermore, basal ganglia seem to be associated not only with the clinical manifestation of the disease but also they might be involved in different cognitive functions commonly impaired in schizophrenia, as they are part of the cortico-striato-thalamocortical circuits, which are central for information processing and attention (Arsalidou et al. 2013). Indeed, although the primary role of basal ganglia has been reported to be the fine regulation of complex movements (Tremblay et al. 2015), recent studies now supported their implication in cognitive functions, including attention, working memory, reward and executive functions (Arsalidou et al. 2013; Rabinovici et al. 2015; Vatansever et al. 2016). This evidence has been also supported by a rodent model of schizophrenia which reported that an imbalance between cortical and subcortical dopamine resulted in severe cognitive deficits (Eyles et al. 2012).
Related Knowledge Centers
- Dopaminergic
- Antipsychotic
- Mesolimbic Pathway
- Mesocortical Pathway
- Broca'S Area
- Wernicke'S Area
- Uncinate Fasciculus
- Cingulate Cortex
- Long-Term Potentiation
- Auditory Cortex