A New Drug for SchizophreniaEssay Preview: A New Drug for SchizophreniaReport this essayA New Drug for SchizophreniaAn individual afflicted by schizophrenia. is attributed to abnormalities in medial temporal brain structure (Mayo Clinic, 2012). Schizophrenia is associated with changes in brain neurochemistry and neuroanatomy. Definitive features of schizophrenia include delusions and having auditory hallucinations. Additional characteristics of this disorder include anxiety, violence, aloofness, verbal confrontations, patronizing manner, anger, and suicidal thoughts or behavior (Mayo Clinic, 2012).
Remington et al. (2011) state that the effective treatment of schizophrenia is comparative to a dopamine blockade of D2 receptors. Research suggests the previously known theory of schizophrenia as being a hyperdopaminergic disorder, where treatment is managed by antipsychotics. In context of the Remington study, schizophrenia is not recognized as a hyperdopaminergic disorder. Rather, it is distinguished as a hypodopaminergic disorder. This new approach in the pathophysiology of the disorder may represent a theoretical shift in how the disorder is researched, but also in how it is treated (Remington, Agid, & Foussias, 2011). Dopamine therapy, not blockage, may be warranted for treating the underlying basis of the disorder.
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How is methylphenidate used to treat hypodopaminia?
It is used for treat the symptoms of depression, in relation to bipolar disorder, with increased efficacy in patients with a history of manic episodes. However, in patients with a history of major depressive disorder, this can result in higher doses of methylphenidate and less efficacy.
In addition, methylphenidate is being found in stimulant medicines (e.g., Valium and MDMA) as well as in synthetic and psychoactive substances (e.g., Ritalin and Methamphetamine).
To understand why methylphenidate is used as a treatment for ADHD, many people and researchers have had difficulty to determine (for better or worse) the effects of methylphenidate on the developing brain.
The results showed that the majority (57%) of those on a list of prescribed stimulants reported adverse side effects. These included:
Increased the risk of brain fog (e.g., increased body temperature and sleep disruption)
Decreased risk of cardiovascular disorders (e.g., elevated heart rate)
The risk of major depressive disorder (metabolic syndrome, major depression)
Decreased risk of anxiety (metabolic syndrome)
The risks of chronic neurodegenerative diseases such as CVD (metabolic syndrome) and diabetes mellitus (metabolic syndrome)
Decreased body fat (% of participants)
Decreased risk of certain degenerative diseases such as certain type of liver disease, Parkinson’s disease and cancer (metabolic syndrome)
Exposure to methamphetamine and methylphenidate can also have an adverse effect on the brain by altering their action on dopamine and serotonin (two critical pathways involved in the motor and cognitive functions of the brain) or releasing dopamine into the brain (methamphetamine can cause the brain to produce “couplespeak”) (Foussias et al., 2004; Fyfe, 2011); this may result in decreased cognitive function (e.g., impaired concentration, impulsivity). Also, methylphenidate can lead to an increased risk of mental health problems (e.g., suicide):
“Depression, schizophrenia, and depression. We found that an increase in the levels of D2 receptors is associated with a reduction as well as protection from depression and anxiety. Although all of our results appear to be compatible with these results, we are surprised by the small sample size in which the effects of methylphenidate were found [as well as the lack of any associations] that does not necessarily support evidence that an increased risk for depression was due to increased risk factor effects on D2 receptor levels. Based on our observations, it may remain possible to suggest one possible mechanism of methylphenidate exposure at high
The design of a new drug for schizophrenia must take into account the main dopamine pathways in the brain and their function. The mesolimbic pathway is associated with reward and cognition, while the nigrostriatal pathway is associated with movement and memory. If schizophrenia were a hypodopamingergic disorder (hence the over the top compensating reward-seeking and problematic behaviors), then offering a dopamine drug designed to attach to D2 receptors should result in a presentation of decreased stereotypic movement disorders, improved catatonic-related movement, and decreased sensory seeking that may occur with seeking conflict or engaging in odd behavior in order to stimulate a natural dopamine rush to the system common to schizophrenics (Rao, Kellom, Reese, Rapoport, & Kim, 2012).
PharmacodynamicsTo be effective in treating this disorder, the new drug must have the following properties:Attach to D2 receptors in the brain;Increase the concentration of brain dopamine in the synaptic gap;Produce metabolites that may be beneficial to the person, such as N-Desmethylclozapine. N-Desmethylclozapine supports the action at several dopamine receptors, and acts as a partial agonist for opioid receptors (Remington, Agid, & Foussias, 2011).
Produce behavioral changes resulting in improved symptoms for the patient.Clinically speaking, this particular action upon behaviors would lead to a reduction in the maladjusted behavior of a person attempting to create a dopamine-elevating situation.
PharmacokineticsThe desired pharmacokinetic properties would be thus:Have a high absorption rate and thus bioavailability rate of at least 70%.Reach peak concentrations quickly.Have an elimination half-life of 14 days, ideally.Not be subject to food or drink restrictions.Therefore the ideal vehicle for a D2 receptor agonist would be one that adds dopamine to the system quickly, and can be sustained in concentration easily. The method of delivery would be a patch worn for 7 days at a