A comparative trial of the decanoates of flupenthixol and fluphenazine.

A double-blind trial was carried out comparing the effects of decanoates of flupenthixol and fluphenazine on the symptoms, ward behaviour and functional capacity in occupational therapy in 51 chronic schizophrenic patients. The patients were carefully selected on the basis of rigid criteria for diagnoses. To exclude nonresponders to neuroleptics the patients were first taken off neuroleptic drugs and only those who appeared to show deterioration were included in the trial. The dosage of drugs was varied according to clinical indications. The length of the trial was initially 4 months and 31 patients were followed for an additional 4 months. To ensure reliability multiple assessments were made at the start and the end of the trial. Most of the statistical tests showed no differences between the treatments, but some of those relating to affective symptoms showed an advantage for flupenthixol as compared with fluphenazine. There were no differences in the incidence of extra-pyramidal side-effects which required treatment in only 32% of the patients on each drug.

The activity of a benzothiopyranoindazole (IA-4 N-oxide) against Schistosoma mansoni infection in rhesus monkeys.

The prophylactic and therapeutic efficacies of IA-4 N-oxide against Schistosoma mansoni in rhesus monkeys (Macaca mulatta) have been evaluated. Ten monkeys were divided into 5 groups of 2 monkeys each. All monkeys were exposed to S. mansoni cercariae on day 0 and treatment groups were established as follows: untreated controls, oral prophylactic administration, intramuscular prophylactic administration, oral therapeutic administration, and intramuscular therapeutic administration. Analysis of parasitologic and pathologic criteria indicate that the compound is most effective when administered as a therapeutic regimen. Complete cures were effected in these monkeys. Prophylactic treatments resulted in a delay in onset of patency and reductions in fecal egg excretion, worm burdens, and tissue damage.

Pharmacokinetic studies on clopenthixol decanoate; a comparison with clopenthixol in dogs and rats.

The release from the depot, hydrolysis and distribution in the organsim as well as the metabolism and elimination of intramuscularly injected clopenthixol decanoate in Viscoleo have been studied in dogs and rats with radioactive as well as non-labelled drug after single as well as repeated administration. The studies clearly demonstrate the depot effect of clopenthixol decanoate given intramuscularly in oil compared to orally administered clopenthixol. The amounts of drug remaining at the site of injection in dogs suggest monoexponential release of drug from the depot and a half-life of 4-5 days. Rapid hydrolysis to clopenthixol in the organism was indicated by in vitro experiments and in vivo findings. Clopenthixol was found to be the main compound in the organism after single as well as repeated doses. The clopenthixol formed by hydrolysis appeared to be metabolized in the same way as clopenthixol given orally i.e. by dealkylation of the side chain and by S-oxide and N-oxide formation. The elimination pattern with predominant fecal excretion also appeared to be the same after clopenthixol and its esterified derivative apart from the reflection in the latter case of the slow release from depot. A rapid exchange in the organism between tritium from the drugs and hydrogen from the body water was demonstrated. This has to be considered in studies with tritium labelled drugs, where estimation of total radioactivity gives the sum of tritium in drug, metabolites and water.

Low mutagenic activity of four hycanthone analogues in Drosophila melanogaster.

Four structural analogues of the antischistosomal drug hycanthone, indicated as IA-3, IA-4, IA-5, and IA-6, were tested for their ability to induce sex-linked recessive lethal mutations in Drosophila melanogaster. The compounds were administered to adult male flies, by abdominal injection or by feeding. Although in some cases a slight enhancement of the mutation frequency was observed, the analogues tested are considerably less mutagenic in this system than hycanthone itself, the concentrations applied being approximately of equal molarity.