ABSTRACT
Pimozide, a diphenylbutylpiperidine neuroleptic which is FDA-approved as a backup treatment for Gilles de la Tourette's syndrome, has been used abroad for many years as a treatment of schizophrenia and has been recently reported to be particularly effective in treating monosymptomatic hypochondriacal psychosis and delusional jealousy. Pimozide may also have a role in the treatment of negative schizophrenic symptoms, pain syndromes, and obsessive compulsive disorder. After reviewing the relevant clinical literature supporting these indications, the authors review preclinical studies that provide points of departure regarding biochemical mechanisms underlying this unique therapeutic profile.
Subject(s)
Pimozide/therapeutic use , Chronic Disease , Clinical Trials as Topic , Delusions/drug therapy , Double-Blind Method , Humans , Obsessive-Compulsive Disorder/drug therapy , Pain/drug therapy , Pimozide/adverse effects , Placebos , Schizophrenia/drug therapy , Syndrome , Tourette Syndrome/drug therapyABSTRACT
Reports over the last 20 years suggest that pimozide, a neuroleptic of the diphenylbutylpiperidine (DPBP) group, might be helpful in the treatment of negative symptoms of schizophrenia, which are considered less responsive to standard neuroleptics than are positive symptoms. Research suggests that neuroleptic drugs of the DPBP group possess a unique property--potent calcium channel antagonism--which could explain their ability to relieve negative symptoms. Earlier reports, however, used measures not specifically designed to assess the negative syndrome. The Positive and Negative Syndrome Scale (PANSS) was developed and standardized to measure the negative syndrome in schizophrenia. The authors used the PANSS to study the effects of pimozide in a 6-week, open clinical trial with 10 neuroleptic-resistant schizophrenic inpatients who had prominent deficit features. Negative but not positive symptoms improved significantly, suggesting that the drug might target the negative profile. The authors discuss possible pharmacologic mechanisms for pimozide's potentially distinct clinical properties.
Subject(s)
Pimozide/therapeutic use , Schizophrenia/drug therapy , Schizophrenic Psychology , Adult , Calcium Channel Blockers , Clinical Trials as Topic , Female , Hospitalization , Humans , Male , Middle Aged , Pimozide/pharmacology , Psychiatric Status Rating Scales , Receptors, Dopamine/drug effects , Schizophrenia/diagnosisABSTRACT
Three cases of a syndrome resembling neuroleptic malignant syndrome are described in patients never exposed to neuroleptics. Each patient had a long history of Parkinson's disease treated with a carbidopa-levodopa combination. Two patients developed the syndrome when administration of the drug was discontinued temporarily. One developed the syndrome before the "drug holiday," and then died during the holiday because of this complication.
Subject(s)
Levodopa/adverse effects , Neuroleptic Malignant Syndrome/etiology , Substance Withdrawal Syndrome , Aged , Humans , Levodopa/therapeutic use , Male , Middle Aged , Neuroleptic Malignant Syndrome/physiopathology , Parkinson Disease/drug therapyABSTRACT
The effects of artificially induced intrauterine growth retardation on hematological values of the rat are manifest only temporarily in the red blood cell number, the amount of hemoglobin, and the 2,3-DPG. These three elements reached normal levels after the fifth day of postnatal life. We believe that this temporary effect may be the consequence of the short-term effect of hydroxyurea (the drug used to produce intrauterine growth retardation) upon DNA synthesis in the hematopoietic system. The animals compensate for the low red cell number and low hemoglobin by raising the levels of 2,3-DPG brought about by the temporary anoxia.
