Dopamine psychoses

Somoza EC, Winhusen TM, Bridge TP, et al An open-label pilot study of methylpheni-date in the treatment of cocaine-dependent patients with adult attention deficit/ hyperactivity disorder. J Addict Dis 23 77—92, 2004 Sora 1, Wichems C, Takahashi N, et al Cocaine reward models conditioned place preference can be established in dopamine- and in serotonin-transporter knockout mice. Proc Natl Acad Sci U S A 95 7699-7704, 1998 Soral, Hall FS, Andrews AM, etal Molecular mechanisms of cocaine reward combined dopamine and serotonin transporter knockouts eliminate cocaine place preference. Proc Nad Acad Sci U S A 98 5300-5305, 2001 Spear J, Alderton D Psychosis associated with prescribed dexamphetamine use 0etter). 

Staley, J.K., Wetli, C.V., Ruttenber, A.J., Heam, W.L., Kung, H.F., and Mash, D.C. Dopamine transporter and receptor autoradiography in cocaine psychosis and sudden death. Biol. Psychiatry. 37 656, 1995. 

With the introduction of chlorpromazine in 1952, there was a small revolution in psychiatry patients suffering from psychosis were able to be de-institutionalized. Chlorpromazine and other typical antipsychotics (e.g., haloperidol) demonstrate high in vitro binding affinities for the dopamine D2 receptor (D2). Specifically, their... 

The answer is d. (Katz ng, pp 464-4670 Adding carbidopa decreases the amount of dopamine that is formed peripherally from dopa by dopa decarboxylase Depression, psychosis, and other psychiatric adverse effects of L-dopa are mediated by CN5 dopamine, so adding carbidopa does not make them less likely The combination of L-dopa and carbidopa reduces the extracerebral metabolism of L-dopa, resulting in decreased peripheral adverse effects. 

Extrapyramidal side-effects generally appear with blockade of dopamine D2 receptors in excess of 80%, whereas clinical efficacy in treating psychosis is associated with 60-70% D2 receptor blockade [12]. Recently, a partial agonist for the D2 receptor known as aripiprazole has been developed, which results in approximately 70% antagonism/30% agonism at the D2 receptor. It is an effective antipsychotic, has low risk for extrapyramidal symptoms, and does not cause elevated levels of prolactin as do the full antagonists at D2 receptors. 

In vivo dialysis studies indicate that acute blockade of the NMDA receptor in experimental animals results in a dis-inhibition of forebrain dopamine-release, suggesting that dopamine-mediated psychosis could be secondary to a more primary defect in cortical glutamatergic signaling. 

Tamminga, C. A. and Carlsson, A. Partial dopamine agonists and dopaminergic stabilizers, in the treatment of psychosis. Curr. Drug Targets CNS Neurol. Disord. 2 141-147, 2002. 

There is less risk of developing motor complications from monotherapy with dopamine agonists than from L-dopa. Because younger patients are more likely to develop motor fluctuations, dopamine agonists are preferred in this population. Older patients are more likely to experience psychosis from dopamine agonists therefore, carbidopa/L-dopa may be the best initial medication in elderly patients, particularly if cognitive problems or dementia is present. 

Common side effects of dopamine agonists are nausea, confusion, hallucinations, lightheadedness, lower-extremity edema, postural hypotension, sedation, and vivid dreams. Less common are compulsive behaviors, psychosis, and sleep attacks. Hallucinations and delusions can be managed using a stepwise approach (Table 55-4). When added to L-dopa, dopamine agonists may worsen dyskinesias. 

Dopaminergic hypothesis. Psychosis may result from hyper- or hypoactivity of dopaminergic processes in specific brain regions. This may include the presence of a dopamine (DA) receptor defect. 

Seeman, P., Weinshenker, D., Quirion, R., et al. (2005) Dopamine supersensitivity correlates with D3 high states, implying many paths to psychosis. Proc. Natl. Acad. Sci. U. S. A. 102, 3513-3518. 

Too Much Neurotransmission. Other mental illnesses result from too much neurotransmission (i.e., overactivity) of certain brain circuits. One example may be psychosis, for example, hallucinations and delusions that have been hypothesized to result from excessive transmission of the neurotransmitter dopamine in certain pathways. In some cases, the transmission becomes so excessive that it kills the nerve cell, a phenomenon called excitotoxicity. This process is believed to occur in some patients with epilepsy and in those with Huntington s disease. 

Antidepressants that increase serotonin activity can also indirectly decrease dopamine activity by inhibiting the activity of dopamine-secreting nerve cells. This effect on dopamine nerve cells is generally not of sufficient magnitude to treat psychosis, but it may explain why patients taking these antidepressants on rare occasions experience akathisia and other extrapyramidal side effects. 

Increased mortality in elderly w/ dementia-related psychosis Uses Schizophrenia Action Dopamine serotonin antagonist Dose Adults. 10-15 mg PO daily 5.25-15 mg for acute agitation Caution [C, -] Disp Tabs, inj SE Neuroleptic malignant synd,... 

The transmethylation hypothesis depended on the psychosis of mescaline as an example of how methylated compounds similar in structure to the monoamine neurotransmitters could be psychotogenic, and demonstrated how methionine, the precursor of the methyl donor S-adenosylmethionine, could exacerbate the psychotic symptoms of schizophrenia in patients. This theory was fed by studies of the now notorious pink spot, an amine found in paper chromatography of urine extracts from schizophrenics and thought to be 3,4-dimethoxyphenylethylamine (i.e., O-methylated dopamine). Subsequent studies eventually identified this as another compound or compounds, primarily of dietary origin. Another methylated derivative erroneously proposed to be found in higher quantities in schizophrenia was dimethyltryptamine. This compound is similar in structure to LSD, the hallucinogenic nature of which was the key to the serotonin deficiency hypothesis, which proposed that the known antagonism of serotonin (5-HT) by LSD indicated that psychotic disorders such as schizophrenia may result from a hypofunction of 5-HT. 

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