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Biomedical subjects

O Svendsen

Publications and source records attributed to O Svendsen.

71 records · Page 4Linked to original sources
PubMed1977

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.

5-Hydroxytryptophan↗
PubMed1977

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.

Adenylyl Cyclases↗
PubMed1977

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.

Administration, Oral↗
PubMed1976

Tissue damage and concentration at the injection site after intramuscular injection of chemotherapeutics and vehicles in pigs.

Intramuscular injection sites were examined for macroscopical and microscopical changes and for residues of drugs six and 30 days after injection of chemotherapeutic preparations or vehicles in swine. The chemotherapeutic preparations contained sulphonamide and/or trimethoprim. All the chemotherapeutic preparations and the vehicles except physiological saline and sterile water caused macroscopical and microscopical changes, mainly appearing as areas of necrotic muscle tissue six days after the injection and as scar tissue 30 days after the injection. Residues of drugs were found at nearly all the injection sites six days after the injection, while 30 days after the injection only residues of sulphonamides were detectable in nearly half of the injection sites.

Animals↗
PubMedDate not supplied

Behavioural correlates to the dopamine D-1 and D-2 antagonists.

The acute dopamine (DA) receptor blockade of neuroleptics can be demonstrated in mice by antagonism of stereotypies induced by the DA-agonist methylphenidate and in rats by antagonism of stereotypies induced by the DA-agonists amphetamine or apomorphine. Neuroleptics such as the thioxanthene, cis(Z)-flupentixol, the phenothiazine, fluphenazine, the butyrophenone, haloperidol and the benzamide clebopride are equipotent behaviourally as well as clinically. Also the D-1 receptor-antagonist SCH 23390 has the same pharmacological effects. In a series of experiments where the methylphenidate-induced stereotyped gnawing in mice was inhibited by neuroleptics it was shown that the effect of butyrophenones was greatly attenuated by concomitant treatment with scopolamine and diazepam. Similar results were obtained in rats experiments. The effect of phenothiazines was less influenced and that of thioxanthenes and SCH 23390 remained nearly unchanged. Besides, a clear differentiation of these drugs was seen when they were tested in mice rendered supersensitive by 12 days treatment with different neuroleptics. In the withdrawal phase the decrease effects against methylphenidate were shown by increased ED50 values for methylphenidate antagonism and an increased response to methylphenidate. The thioxanthenes and SCH 23390 retained the ability to antagonize the stereotyped gnawing, the phenothiazines showed a reduced effect, whereas the butyrophenones showed both tolerance and cross tolerance to the stereotyped behaviour. This behavioural classification of neuroleptics into three different groups is comparable with the classification obtained by DA-receptor binding techniques in vitro.

Adenylyl Cyclases↗