Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When tested in rats supersensitive to dopamine agonists, the atypical neuroleptic clozapine displayed pharmacological properties expected of both a D-1 and D-2 receptor antagonist. The locomotor response induced by the D-1 receptor agonist SKF-38393 in neonatal-6-hydroxydopamine (6-OHDA)-lesioned rats was reversed in a dose-related fashion, although a complete blockade of this behavior was not observed indicative for only a partial antagonism of D-1 receptor function. Clozapine also blocked the self mutilation resulting from L-dihydroxyphenylalanine (L-DOPA) administration to neonatal-6-OHDA-lesioned rats, an effect previously linked to D-1 receptor activation. At higher doses, clozapine blocked the locomotor activity elicited by the D-2 agonist LY-171555 in adult-6-OHDA-lesioned rats. Therefore, the action of clozapine on D-1 as well as D-2 receptor-mediated behaviors contributes to its pharmacological effects. The ability of clozapine to stop self-mutilatory behavior in neonatal-6-OHDA-lesioned rats suggests that this drug might be an effective treatment for self-injurious behavior associated with the Lesch-Nyhan syndrome and mental retardation.
 ...
PMID:Clozapine antagonism of D-1 and D-2 dopamine receptor-mediated behaviors. 249 73

Few investigators have focused on the response of individuals with mental retardation to clozapine. In the general population, some people who have responded to no other psychotropic have had a tremendous positive response, including increased positive scores "quality of life" measures. Clozapine, however, can cause fatal side effects. At least six people in the United States have died from agranulocytosis despite weekly blood counts. The use of clozapine in the general population was reviewed, potential difficulties in prescribing it for individuals with mental retardation discussed, and three relevant case histories presented.
 ...
PMID:Clozapine in three individuals with mild mental retardation and treatment-refractory psychiatric disorders. 798 16

Clozapine-use patterns in facilities operated by the Texas Department of Mental Health and Mental Retardation are reported. Data collected by manual and automated tracking systems from January 1990 through July 1992 were analyzed to determine patient demographics, the number of patients started on clozapine and the number who stopped taking the drug, the reasons for discontinuation, and other variables. Of 852 clozapine recipients still in the departmental system by the end of the study period, 134 (16%) had discontinued the drug by that date. There were no significant differences in gender, age, or race between the patients who discontinued the therapy and those who did not. Almost one fourth of the patients who discontinued clozapine therapy did so within the first month, and more than 90% did so within the first year. The most common reasons for discontinuing the medication were lack of clinical response, patient refusal or request, and adverse effects, including agranulocytosis. More women than men discontinued the drug because of adverse effects. Although relatively few patients discontinued clozapine during the study period, many had only recently begun taking the drug, and some of these may discontinue it in the near future. Of 852 clozapine-treated patients served by the Texas Department of Mental Health and Mental Retardation between January 1990 and July 1992, 16% discontinued the therapy. One fourth of these did so within the first month of treatment.
 ...
PMID:Use of clozapine in Texas state mental health facilities. 836 20

Neuroleptic and anticonvulsant drugs are used to reduce the occurrence of aberrant behaviors, seizures, or both in individuals with mental retardation. However, their use may disrupt the learning of desired skills, and the extent to which anatomical (e.g., microencephaly) or biochemical abnormalities or both in such individuals alter the effects of drugs on learning is not known. In this study, the effects of neuroleptics and anticonvulsants on learning and performance in a repeated acquisition task in methylazoxymethanol-induced microencephalic and saline control rats were assessed. Thioridazine was more potent in microencephalic rats than in control rats in increasing errors and decreasing response rates. Clozapine was equally potent in both microencephalic and control rats in increasing errors and decreasing response rates. The effect of carbamazepine was biphasic in both rat groups: Low doses decreased errors and increased response rates, whereas higher doses did the opposite.
 ...
PMID:Effects of neuroleptic and anticonvulsant drugs on repeated acquisition learning in microencephalic and normal rats. 938 59

This study reports a clinical experience among twenty schizophrenic patients treated by clozapine during two years and eight months within a range extending from three months to seven years. These twenty patients had previously shown long-term resistance to usual neuroleptics but three out of them met the diagnosis of mental retardation or childhood disintegrative disorder (F.84.3-ICD 10). These patients were put under clozapine for their violent behavior. The methodology was retrospective, descriptive with intra-individual comparison, each patient being his own reference before and after treatment. Diagnosis met CD 10 criteria and were assessed without using standard examination. This study aimed at assessing once more clozapine efficacy and tolerance upon a long time follow up. Single therapy has been the rule and dosages have been progressively increased reaching a mean daily dosage of 350 mg per day. The efficacy, assessed by the way of BPRS, GAF (DSM III-R) and simplified form of CGIS, has been verified in approximately 30% of the patients, mainly concerning positive symptoms. Clozapine was also able to alleviate severe behavior troubles brought about by delusional states, without this latter being markedly softened when it was a long term one. Clozapine tolerance has shown it to be satisfactory, however we noticed the occurrence of a leucopenia with neutropenia after seventeen weeks of treatment, followed, some days later, by a Quincke oedema, which forced to interrupt the treatment. White blood cells came back in a normal range fifteen days later. The other side effects (transitory hypersialorrhea, tachycardia, without clinical and ECG perturbations) have been usually well tolerated and have never caused treatment interruption. No extrapyramidal side effect have been noticed among our twenty patients. The end of this paper consists in the presentation of four clinical cases: one about the efficacy of clozapine upon violent antisocial behaviour in a schizotypital disorder; one delusional chronic schizophrenic patient whose violence has been controlled despite of the delusion; one paranoid schizophrenic patient who has been able to maintain a satisfactory professional and family adaptation; and finally a childhood disintegrative disorder (F.84.3-ICD 10) in whom occurred the only leucopenia side effect of our study. These four clinical cases have seemed particularly meaningful regarding our clinical experience of clozapine which has been lasting for almost seven years now.
 ...
PMID:[Long-term clinical experience with clozapine]. 945 32