benztropine and fluphenazine-enanthate

The neuroleptic malignant syndrome (NMS) is a rare but potentially lethal disorder associated with the administration of neuroleptic agents. This syndrome may be underdiagnosed because it is poorly understood and often unrecognized. It affects all age groups and has a 20% mortality. Presenting features include extrapyramidal symptoms, altered mental consciousness, autonomic dysfunction, and hyperthermia. The underlying explanation for these manifestations is a disturbance of the dopaminergic system within the basal ganglia and hypothalamus. Dantrolene (Dantrium), amantadine (Symmetrel), and bromocriptine mesylate (Parlodel) have been efficacious in conjunction with supportive therapy. I report three cases successfully treated with bromocriptine and supportive therapy.

Topics: Adolescent; Adult; Benztropine; Bromocriptine; Catatonia; Child; Child, Preschool; Diagnosis, Differential; Female; Fluphenazine; Haloperidol; Heat Exhaustion; Humans; Male; Malignant Hyperthermia; Middle Aged; Neuroleptic Malignant Syndrome; Psychotic Disorders; Schizophrenia, Paranoid; Time Factors

Two different studies were performed in subhuman primates in an attempt to induce symptoms of tardive dyskinesia. The first study lasted for over 5 years. This involved elderly Macaca speciosa. The animals were given first 25 mg of fluphenazine decanoate and later the enanthate IM (3.2 mg/kg) every 2 weeks and on 5 days a week, haloperidol, first IM and later PO. Haloperidol was given first in doses of 1.0 mg/kg and ultimately after years of therapy, in doses of 6.4 mg/kg per day. Those animals who survived gained weight to over 10 kg. After neuroleptic withdrawal, tardive dyskinesia became evident in 1 month. The symptoms of tardive dyskinesia following cessation of medication lasted a maximum of 1 year. This animal model produced very impressive symptoms in one of the three animals treated who survived. This is not a very practical animal model from the aspects of economics (costly), time (5 years), and animal availability (rare and endangered species). However, the symptoms of tardive dyskinesia are very striking and identical with human tardive dyskinesia in a susceptible animal. A more practical experimental animal model involved Cebus apella. Depot fluphenazine (0.1 to 3.2 mg/kg) was given continuously every 2 weeks for 1 year. In this species the symptoms of tardive dyskinesia became progressively prolonged and intense with each course of fluphenazine therapy and withdrawal, suggesting that reversible tardive dyskinesia may turn into irreversible tardive dyskinesia. With each succeeding course of fluphenazine therapy (1 month) and withdrawal (1-3 months), the animals appeared to be sensitized to both the acute extrapyramidal and the tardive dyskinesia symptoms. These animals were also given various experimental drug treatments including biperiden lactate, benztropine mesylate, and d-amphetamine after they developed signs of tardive dyskinesia.

Topics: Animals; Antipsychotic Agents; Benztropine; Cebus; Death, Sudden; Disease Models, Animal; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Fluphenazine; Haloperidol; Humans; Macaca; Male; Motor Activity; Stereotyped Behavior; Substance Withdrawal Syndrome

Topics: Animals; Benztropine; Biperiden; Cebus; Disease Models, Animal; Dyskinesia, Drug-Induced; Female; Fluphenazine; Macaca; Male; Parasympatholytics; Species Specificity; Syndrome