title: Evidence of brain dopamine deficiency in schizophrenia.
abstract: It is proposed that the increased dopamine function suggested by the dopamine hypothesis of schizophrenia is a dopaminergic postsynaptic receptor supersensitivity resulting from a dopamine deficiency. In support of this, three double-blind controlled studies conducted on drugs which alter brain dopaminergic activity in a manner different from that of classic neuroleptics are reported. 1) alpha-methyldopa-neuroleptic interaction proved efficacious for schizophrenic positive symptoms but only on a short-term basis. 2) Rubidium improved negative symptoms rapidly, and in contrast has a late onset of action on positive symptoms of schizophrenia. 3) Tryptophan-benserazide was efficacious in controlling both negative and positive symptoms of schizophrenia (although less so than chlorpromazine). It is concluded that currently accepted modes of pharmacological therapy (classical neuroleptics) are in the short-term controlling the dopamine supersensitivity secondary to a deficiency, but contributing in the long-term to increase the dopamine deficiency, and so exacerbate the supersensitivity. More effective forms of treatment may involve the use of agents which alter dopamine activity without inducing dopamine supersensitivity.
mesh_terms: D001545:Benserazide / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism*; D002746:Chlorpromazine / Q000627:therapeutic use; D004298:Dopamine / Q000172:deficiency*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D008750:Methyldopa / Q000627:therapeutic use; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012413:Rubidium / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D014364:Tryptophan / Q000627:therapeutic use
chemical_list: D011954:Receptors, Dopamine; D012701:Serotonin; D008750:Methyldopa; D001545:Benserazide; D014364:Tryptophan; D012413:Rubidium; D002746:Chlorpromazine; D004298:Dopamine