Dopamine schizophrenic symptoms

In 1976, Ian Creese, David R. Burt, and Solomon H. Snyder of Johns Hopkins University in Baltimore, Maryland, reported that the most effective schizophrenia medications are the ones that have the strongest affinity for dopamine receptors. Researchers also discovered drugs that increased the amount of dopamine inadvertently caused schizophrenic symptoms in patients. These findings led to the dopamine hypothesis of schizophrenia—too much dopamine causes schizophrenia. 

The dopamine-blocking activity of neuroleptic drugs can antagonize the effects of dopamine receptor agonists, such as bromocriptine. Conversely, bromocriptine has been reported to cause exacerbation of schizophrenic symptoms (633). 

It is believed that although antipsychotic medications block norepinephrine, serotonin, and acetylcholine, their primary action is as central dopamine antagonists (Galenberg, 1991 Meyer Quenzer, 2005). That is, these drugs block central dopamine receptors, particularly the Dj subtype, and thus inhibit dopaminergic neurotransmission in the brain. The postsynaptic receptor blockade in the limbic system is thought to reduce the schizophrenic symptoms. 

Drug-induced psychosis can occur without activation of brain dopamine receptors All effective antipsychotic dmgs have high affinity for dopamine D2 receptors Fluphenazine has been prescribed for a 20-year-old male patient. His schizophrenic symptoms have improved enough for him to reside in a halfway house in the community. He visits his physician with a list of complaints about his medication. Which one of the following is not likely to be on his list ... 

Areca may interact adversely with antipsychotic medications (Deahl 1989). Two cases have been reported of schizophrenic patients who were taking neuroleptics and developed severe extrapyramidal symptoms after areca chewing. Given the functional antagonism between dopamine and acetylcholine in the striatum, it is likely that arecoline amplified the dyskinetic effect of neuroleptic medications. 

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. 

It is well known that typical neuroleptics, all of which have a high affinity for dopamine receptors (particularly D2 receptors), do not effectively treat all schizophrenic patients and have only limited beneficial effects on the negative symptoms of the illness. Furthermore, neither typical nor atypical neuroleptics have an immediate effect on the positive symptoms even though it can be shown by both experimental studies in animals and by imaging methods in schizophrenic patients that neuroleptics rapidly bind to dopamine receptors. Thus factors other than an overactive dopaminergic system are probably operative in this disorder. The question is which of the numerous neurotransmitters and modulatory neuropeptides are responsible for both the negative symptoms and the delay in onset of the therapeutic effects of neuroleptics on the positive symptoms ... 

In addition to acute and chronic schizophrenia, the neuroleptics are sometimes used in the management of mania, delirium, and severe agitation, whatever the cause of these symptom complexes. It must be noted that unlike parkinsonism, where a definite dysfunction in the DA system has been established, for schizophrenia and other psychiatric diseases, no unequivocal evidence has yet been presented to prove that there is a disturbance of the DA system (e.g., dopaminergic overactivity or receptor hypersensitivity). In untreated schizophrenics the production of DA metabolites is normal. Conflicting results have been obtained in studies of the DA receptors in schizophrenics (11,12,13), but in the case of patients who have not received neuroleptics, the receptor density and affinity appear to be normal (13). The "dopamine hypothesis" in these disorders derives from the beneficial effects of drugs that block DA receptors. 

Circunstantial evidence directly implicating dopamine in the pathogenesis of duodenal ulcer in man is the unusual incidence of peptic ulcer disease in dopamine-deficient disorders. From purely descriptive clinical and epidemiologic studies we know that patients with Parkinson s disease, before the introduction of dopamine therapy, had an excess of ulcer disease (72). One report even comments on the curiosity that after initiation of L-DOPA administration the ulcer symptoms have virtually disappeared (72 ). On the other hand, less clearly, schizophrenia which is associated with dopamine excess and/or receptor hyperactivity is accompanied by virtual lack, or decreased prevalence, of peptic ulcer (73-76). Schizophrenia associated with ulcer disease has been viewed as a reportable curiosity in medical literature (75). At present, possibly because of the widespread therapeutic application of neuroleptics, the lack of peptic ulcer disease in schizophrenics is less striking than in the past. On the other hand, we recently observed in our autopsy series perforated duodenal ulcers in two schizophrenic patients who had been on large doses of haloperidol therapy (Szabo, unpublished observation). Thus, even in man, dopamine may indeed be implicated in the pathogenesis of duodenal ulcer disease. 

Glenthoj BY, Mackeprang T, Svarer C, Rasmussen H, Pinborg LH, et al. 2006. Frontal dopamine D(2/3) receptor binding in drug-naive first-episode schizophrenic patients correlates with positive psychotic symptoms and gender. Biol Psychiatry 60 621-629. 

Heinz A, Knable MB, Coppola R, Gorey JG, Jones DW, Lee KS, Weinberger DR. Psychomotor slowing, negative symptoms and dopamine receptor availability—an IBZM SPECT study in neuroleptic-treated and drug-free schizophrenic patients. Schizophr Res 1998 31(l) 19-26. 

The second observation is that drugs that increase dopamine activity (such as amphetamines) can product a paranoid psychosis similar to paranoid schizophrenia and, if given to schizophrenic patients, amphetamines may exacerbate psychotic symptoms. 

Although several tlieories address the action of antipsychotics, the dopamine hypothesis is generally accepted. This theory is based on the observation of amphetamine-induced psychosis, which serves as a pharmacological model of schizophrenic behavior. The symptoms evidenced in this model psychosis are readily ameliorated through the... 

No article was found reporting anxiolytic activity of phenolic acids. However, the anxiolytic activity of the alkaloids is known. Anxiolytic properties may be a crucial feature of newer antipsychotics associated with the improvement of negative symptoms in schizophrenic patients. The indole alkaloid alstonine acts as an atypical antipsychotic in behavioral models, but differs in its dopamine and serotonin binding profile [310]. Behavioral effects of psychollatine, a glycoside indole monoterpene alkaloid isolated from Psychotria umbellate Thoim., was investigated in models of anxiety, depression, memory, tremor, and... 

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