A double-blind comparison of acitretin and etretinate in the treatment of Darier's disease.

The objective of this double-blind study was to compare the therapeutic effects of acitretin with those of etretinate in patients with Darier's disease. Twenty-six patients (10 males and 16 females) were included in the study. Patients were treated with 30 mg daily for the first 4 weeks and with an individually adjusted dose (10-50 mg/day) for the subsequent 12 weeks. Remission or marked improvement was obtained in 10 of the 13 acitretin-treated patients and in 8 of the 11 etretinate-treated patients who completed the 16-week treatment. The usual mucocutaneous adverse reactions of retinoids were observed in all but one patient. There were no significant differences between treatment groups with regard to the incidence of these reactions.

An investigation into the floating behaviour of a pectin-containing anti-reflux formulation (FF5005) by means of gamma scintigraphy.

The gastric distribution and residence time of a new pectin-containing formulation, FF5005 (Farma Food A/S, Denmark), was investigated by using the technique of gamma scintigraphy in six healthy volunteers after administration with a radiolabelled meal. The formulation and test meal were radiolabelled with indium-113m and technetium-99m, respectively, and the formulation was administered to the subjects 30 min after the labelled meal. FF5005 was shown to float and form a discrete phase on top of the stomach contents and emptied from the stomach more slowly than the food (p less than 0.05, Wilcoxon signed rank test). The times taken for the formulation and test meal to half-empty from the stomach (T50) were 4.13 +/- 0.69 h (mean +/- SD) and 2.17 +/- 0.15 h (mean +/- SD), respectively. Greater than 50% of the formulation remained in the fundal region of the stomach for 3 h. FF5005 produced in vivo behaviour similar to that of established alginate-containing anti-reflux agents, and the pectin content of the formulation was shown to decrease the rate of emptying of the meal.

High-dose metoclopramide in the treatment of cis-platinum induced emesis. A dose-finding study.

In 92 patients receiving 270 cytostatic courses which all included cis-platinum, the antiemetic efficacy of medium- or high-dose metoclopramide was investigated. Metoclopramide was given intravenously 4 times during a 6-hour period (1/2 h before and 1 1/2, 3 1/2 and 5 1/2 h after cytostatic treatment) in a total dose of 1, 2, 4, 6, or 8 mg/kg. Nausea, emetic episodes, and side effects were registered during 24 h. The 1 mg/kg dose was given in 20 courses for which the average of emetic episodes was 16. In the four higher dosed groups the averages were 8, 8, 5, and 6, respectively. The average number of emetic episodes was significantly higher (p less than 0.001) in the 1 mg/kg metoclopramide group than in the 250 higher dosed courses. The frequency of side effects seemed independent of the dose in the interval 2-8 mg/kg while diarrhoea and other side effects tended to be less frequent in the 1 mg/kg metoclopramide group. Since antiemetic effect of metoclopramide in the dose interval 2-8 mg/kg did not increase with the dose, it is recommended to treat cis-platinum-induced emesis with 2 mg/kg metoclopramide given intravenously as 4 doses during a 6-hour period.

Serum concentrations of the isomers of clopenthixol and a metabolite in patients given cis(Z)-clopenthixol decanoate in viscoleo.

Cis(Z)-clopenthixol decanoate in Viscoleo (Sordinol Depot, Cisordinol Depot, Clopixol Inj.) was given intramuscularly to nine schizophrenic patients with dosage intervals of 1 or 2 weeks. Serum concentrations of the two geometric isomers of clopenthixol and its N-dealkyl metabolite were recorded in two successive dosage intervals. Significant correlations were found for dose vs area under the serum concentration curve and vs serum concentrations measured on individual days. The last mentioned concentrations are good measures of the area under the serum concentration curve, which expresses the drug load of the patient. The serum concentration curves in two successive dosage intervals were very similar. Maximum serum concentration was seen 5-7 days after injection and the mean maximum/minimum fluctuation was 1.6 with the 2-week dosage interval. The finding of very low amounts of the trans(E)-isomers of clopenthixol and the N-dealkyl-metabolite shows that isomerization of the cis(Z)-compounds into the corresponding trans(E)-isomers does not take place within the organism.

The pharmacology of a new potent, long acting neuroleptic, piflutixol.

Piflutixol, 6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene, has been shown to have pronounced neuroleptic properties. It is a very potent inhibitor of methylphenidate-induced stereotypies in mice, amphetamine and apomorphine-induced stereotypies in rats, apomorphine-induced stereotypies and vomiting in dogs. Furthermore piflutixol causes cataleptic reaction in small doses and inhibits conditioned avoidance reaction in rats. The compound is equally potent orally and parenterally and has a prolonged effect. Piflutixol has up to the present proved to be the most potent inhibitor of dopamine-stimulated adenylate cyclase in rat striatum in vitro. Piflutixol has a stron sedative effect (inhibition of spontaneous motor activity, induction of ptosis and potentiation of barbiturate anaesthesia) and in addition inhibits reticular arousal reaction in very low doses. Thus piflutixol constitutes a unique combination of potent anti-stereotyped activity with potent sedative effects. This means that piflutixol may prove to be a low-dose basic neuroleptic with long duration of action.

Pharmacology of cis(Z)-clopenthixol decanoate, a depot neuroleptic.

The duration and intensity of the neuroleptic effect of cis(Z)-clopenthixol decanoate in Viscoleo have been compared with those of cis(Z)-clopenthixol, 2 HCl in aqueous solution in a number of animal experimental models. Cis(Z)-clopenthixol, 2 HCl had a strong, but short-lasting neuroleptic effect (apomorphine antagonistic effect in dogs, inhibition of conditioned avoidance response in rats) which was accompanied by marked sedation. In contrast, cis(Z)-clopenthixol decanoate in oil had an effect which was slower in onset, but of much longer duration and only the highest doses caused a slight sedation. In rats catalepsy could be induced in some animals by high doses of cis(Z)-clopenthixol decanoate whereas cis(Z)-clopenthixol, 2 HCl at all the doses tested caused catalepsy in all animals. In mice only high doses of cis(Z)-clopenthixol decanoate in oil caused reduction of spontaneous motor activity and potentiation of barbiturate anaesthesia. The results are discussed with special reference to the clinical use of the depot preparation.

Pharmacology of a new phthalane (Lu 10-171), with specific 5-HT uptake inhibiting properties.

The pharmacological profile of a new bicyclic substance, Lu 10-171 (1-(3-(dimethylamino)propyl)-1-(p-fluorophenyl)-5-phthalancarbonitril), is described and compared with that of existing tricyclic thymoleptics. In mice and rats the compound exhibited marked 5-HT potentiating properties both in vivo and in vitro, being 5-10 times as active as chlorimipramine. The tests included 5-HT-, 5-HTP- and tryptophan-potentiation. In monoamine oxidase inhibitor treated dogs and rabbits the compound caused a marked hyperthermia. In rabbits this effect was completely blocked by pretreatment with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine. Hyperthermia induced by the central catecholamine displacing substance H 77/77 in rats was not affected by Lu 10-171, whereas the substance abolished the temperature rise induced by H 75/12. Reserpine- and tetrabenazine-induced ptosis and tetrabenazine-induced immobility in mice were antagonized by relatively low doses of existing tricyclic thymoleptics, whereas Lu 10-171 was very weak in this respect. Very weak in vitro anticholinergic and antihistaminergic properties were also registered for Lu 10-171. It is concluded that Lu 10-171 is a very potent and highly specific potentiator of 5-HT both in vivo and in vitro probably due to inhibition of 5-HT uptake. Thus this compound might be a useful agent in studying the role of 5-HT neurone systems in the control of mood. The substance does not possess the NA potentiating and anticholinergic and antihistaminergic properties characteristic of the tricyclic antidepressants.