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Biomedical subjects

O Svendsen

Publications and source records attributed to O Svendsen.

At least 55 records · Page 3Linked to original sources
PubMed1984

Pharmacological effects of a specific dopamine D-1 antagonist SCH 23390 in comparison with neuroleptics.

Neuroleptics such as thioxanthenes (cis(Z)-flupentixol and cis(Z)-clopenthixol) and phenothiazines (fluphenazine and perphenazine), which block both dopamine (DA) D-1 and D-2 receptors and the butyrophenones (haloperidol and spiroperidol), which block D-2 receptors only, are equipotent both behaviorally and clinically. A new compound SCH 23390 which selectively blocks DA D-1 receptors, resembles many neuroleptics in its pharmacological profile: antistereotypic effects in mice, rats and dogs, cataleptogenic effect and inhibitory effect on amphetamine circling. In contrast SCH 23390 has no effect on apomorphine-induced vomiting in dogs and little effects on 6-OHDA-denervated supersensitive DA receptors, stimulated by the DA agonist 3-PPP. In a series of experiments where methylphenidate-induced stereotyped gnawing in mice was inhibited by neuroleptics, it was shown that concomitant treatment with scopolamine or diazepam attenuated the effect of butyrophenones (D-2 antagonists). The same treatment attenuated the effect of phenothiazines, to a lesser extent, and hardly attenuated the effect of thioxanthenes and SCH 23390 at all. It is concluded that DA D-1 receptors are as important as D-2 receptors for the expression of neuroleptic activity in most animal models believed to be predictive of antipsychotic and extrapyramidal side-effect potential. However, the D-1 antagonist is less sensitive than D-2 antagonists to antimuscarinic compounds and benzodiazepines.

Adrenergic alpha-Antagonists↗
PubMed1984

Intramuscular injections and muscle damage: effects of concentration, volume, injection speed and vehicle.

An intramuscular injection was given to rabbits with the needle inserted in the longissimus dorsi muscle. The muscle tissue at the injection site was examined post-mortem 3 days after the injection and areas of necrotic muscle tissue were dissected for weighing. With a fixed dose of the neuroleptic drug cis(Z)-clopenthixol it was shown that a small volume of a concentrated solution caused less muscle damage than a larger volume of a relatively less concentrated solution. Injection speed, on the other hand, was not an important factor. Aqueous solutions of neuroleptic drugs caused local muscle damage which was diminished or prevented by oily vehicles.

Animals↗
PubMed1983

Dopamine receptor agonistic and antagonistic effects of 3-PPP enantiomers.

The pharmacological profile of the enantiomers of the proposed selective dopamine (DA) autoreceptor agonist 3-PPP [3-(3-hydroxyphenyl)-N-n-propylpiperidine] has been studied. In vitro both enantiomers showed weak DA agonistic activity, and (--)-3-PPP some DA antagonistic effect on DA-stimulated adenylate cyclase activity. Both enantiomers in low doses had a similar profile in vivo: Inhibition of locomotor activity of mice and rats, induction of contralateral circling behaviour in 6-hydroxy-DA-lesioned rats and an emetic effect in dogs. At higher doses, differential effects of the enantiomers were found: (+)-3-PPP induced hyperactivity, weak stereotyped behaviour and ipsilateral circling in hemitransected rats. (--)-3-PPP had depressant effects in high doses, inhibited d-amphetamine-induced hyperactivity and d-amphetamine-, methylphenidate- and apomorphine-induced stereotyped licking/biting in rats and antagonized apomorphine-induced emesis in dogs. However, (+)-3-PPP also showed a weak antagonistic activity against d-amphetamine-induced hyperactivity and d-amphetamine- and apomorphine-induced stereotypy in rats and inhibited apomorphine-induced emesis in dogs. It is suggested that both enantiomers have significant effects on postsynaptic DA receptors in high doses: (--)-3-PPP with weak antagonistic activity in some test models and (+)-3-PPP with agonistic and antagonistic effect. Since these effects of (+)-3-PPP were of low intensity at high doses, (+)-3-PPP may be a partial DA agonist at postsynaptic receptors in high doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1983

Local muscle damage and oily vehicles: a study on local reactions in rabbits after intramuscular injection of neuroleptic drugs in aqueous or oily vehicles.

The local muscle damaging effect of a series of neuroleptics formulated in water or in oily vehicles (Viscoleo, sesame oil, methyl oleate or squalane) has been investigated after intramuscular injection in rabbits. Each drug preparation (2 ml) was administered intramuscularly in the central part of the longissimus dorsi muscle of four rabbits. The rabbits were killed three days after the injection, and the injection site was examined macroscopically. Areas of necrotic muscle tissue were isolated by dissection and weighed. All preparations in aqueous solution caused local muscle damage (large necrotic area) at the injection site. This effect was almost completely neutralized by the Viscoleo vehicle. The sesame oil, methyl oleate and squalane vehicles also neutralized the local damaging effect, but not to the same extent as that of the Viscoleo vehicle.

Animals↗
PubMed1982

Pharmacodynamic effects and possible therapeutic uses of THIP, a specific GABA-agonist.

THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol) is a potent and specific GABA receptor agonist which does not influence the GABA uptake system or GABA metabolizing enzymes. The specificity for the GABA receptor is also demonstrated by lack of action on monoaminergic, cholinergic, histaminergic or opiate receptors. Since in recent years GABA receptor stimulants-among others THIP--have become available many have speculated as to what clinical indication GABA-ergic stimulation might be an important element. The first suggestion was that GABA-ergic drugs by an inhibitory effect on the dopamine neurons would improve the antischizophrenic effect of neuroleptics and improve tardive dyskinesia. Furthermore, studies on brains of deceased Parkinson and Huntington's chorea patients have demonstrated a low level of GABA and its synthesizing enzyme glutamic acid decarboxylase (GAD) in the basal ganglia. Also in epilepsy and diseases with dementia a deficit in the GABA system has been proposed. Therefore a therapeutic strategy for these diseases may be supplementary treatment with drugs which increase GABA receptor activity. Furthermore, recent results in humans have shown that GABA agonists perhaps also could be of benefit in mania and depressions. When considering the neurophysiological elements of nociception and muscle tone it is also reasonable to suggest that GABA-ergic stimulation may reduce pain perception and muscle tone.

Analgesics↗
PubMed1982

Studies on acute toxicity and drug levels of citalopram in the dog.

Electrocardiographic and haemodynamic changes have been studied in conscious dogs after a sublethal oral dose (20 mg . kg-1) of citalopram. Furthermore, the effects of continuous intravenous infusion of citalopram (10 mg . kg-1 per hour) have been studied in conscious and anesthetized dogs. The findings have been related to plasma levels of citalopram. Severe convulsive attacks occurred in conscious dogs after infusion of 21.3 or 26.5 mg . kg-1 and after the oral dose. The convulsions were successfully treated with diazepam. In contrast convulsions were not seen in the anesthetized dogs. They died from respiratory arrest after infusion of 42.2 or 61.3 mg . kg-1. Atrioventricular and intraventricular conduction was unchanged and electrocardiographic changes were negligible. Sinus tachycardia which could be reversed by diazepam and moderate haemodynamic changes were seen. Since no electrocardiographic changes were seen in conscious dogs even during pauses in the convulsive seizure it is concluded that citalopram does not exert cardiotoxic effects in the dog. Good correlation was found between general clinical findings and citalopram levels in plasma. Conscious dogs were exposed to drug levels exceeding those of the average patient by a factor of about 20, while anesthetized dogs had considerable higher concentrations.

Administration, Oral↗
PubMed1979

Long term effect of teflutixol on apomorphine-induced stereotypy and vomiting in dogs.

Dose--response relationships to apomorphine-induced vomiting and stereotyped running behaviour have been determined in dogs before, and up to 24 and 28 days respectively, after daily oral treatment with 2.5 mg/kg of teflutixol or 12 days. The ED50 values for apomorphine-induced vomiting after teflutixol were not different from those obtained before treatment. Stereotyped running behaviour of increasing intensity was seen 4--12 days after teflutixol treatment. The intensity then declined and returned to normal. The results suggest that the nigro-neostriatal dopamine system in dogs became hypersensitive after prolonged teflutixol treatment, while the dopamine receptors of the emetic chemotrigger zone did not.

Animals↗
PubMed1979

The loss of creatine phosphokinase (CK) from intramuscular injection sites in rabbits. A predictive tool for local toxicity.

The CK activity was measured in muscle tissue taken from the injected area (dorsal longissimus muscle) and the contralateral side of the injection site 72 hours after intramuscular injection into rabbits of 1 ml of different dilutions of propylene glycol or glycerol formal in distilled water or 0.9% saline. The total loss of CK activity from the injection site was calculated as the difference between the CK concentration in the normal muscle tissue and that of the injection site from the same animal. From the results the arbitrary amount of muscle tissue depleted of CK activity was further calculated and compared with the severity of the gross pathological findings. A large necrotic area at the injection site was present in all samples with more than 1 g of muscle tissue depleted of CK activity. Minor and probably acceptable pathological changes were found in samples with less than 1 g of muscle tissue depleted of CK activity. The local damaging effect of drug preparations for intramuscular use can thus be evaluated from the calculated amount of muscle tissue depleted of CK activity.

Animals↗
PubMed1978

Hepatotoxicity of citalopram in rats and first-pass metabolism.

A chronic oral toxicity study of citalopram in rats revealed dose dependent hepatic fatty infiltrations in male rats while female rats were unaffected. Subsequent studies demonstrated markedly reduced availability due to first-pass hepatic metabolism in male rats and roughly complete availability in females. Pretreatment of male rats with phenobarbital for 2 weeks caused increased metabolism and simultaneous administration of phenobarbital and citalopram gave more pronounced fatty infiltrations than citalopram alone. A connection is suggested between the first-pass metabolism in male rats and the hepatotoxicity, which is possibly mediated through a metabolite or intermediate formed in toxic amount during the first passage of the liver.

Administration, Oral↗
PubMed1978

A comparative study of serum creatine phosphokinase (CPK) activity in rabbits, pigs and humans after intramuscular injection of local damaging drugs.

Serum creatine phosphokinase (CPK) activity has been determined before and after intramuscular injection of lidocaine, diazepam or saline in humans and lidocaine, diazepam, digoxin and saline in pigs and rabbits. Two ml volum of each of the drugs was given to humans as well as to the experimental animals. No changes in CPK activity were found after saline in humans or rabbits but a minor increase was demonstrated in pigs. A marked increase of CPK activity was demonstrated after lidocaine or diazepam in humans and after lidocaine, diazepam or digoxin in pigs and rabbits. Post mortem examination of the injection sites in the animals revealed extensive muscle tissue necrosis after lidocaine, diazepam and digoxin. No damage of the tissue was found after saline. CPK activity was also determined in rabbits receiving 2 ml of dilutions of diazepam in saline. The injection sites were examined post mortem. The CPK activity was increased in animals receiving 1:2 and 1:8 dilutions while a 1:20 dilution did not give rise to changes in the enzyme activity. The necrotic area diminished when diazepam was diluted and no pathological changes were found at the injection sites after the 1:20 dilution. Measuring the CPK activity in rabbits after an intramuscular injection seems to be a sensitive method for the determination of local toxicity.

Animals↗
PubMed1978

Studies on Tyzzer's disease in rats.

An outbreak of an epidemic disease occurred in a specified-pathogen-free (SPF) breeding colony of rats. The clinical signs and the post-mortem findings were characteristic for Tyzzer's disease. The causative agent, Bacillus piliformis, was demonstrated microscopically in ileum, liver and myocardium, and transmitted to mice where its pathogenicity appeared to be similar to that of another strain isolated from mice. B. piliformis from spontaneously-infected rats was demonstrated by indirect immunofluorescence technique. By means of the same technique it was found that the fluorescence antibody titre obtained of the individual sera from spontaneously-infected mice, rats and rabbits was the same, whether the antigen employed was organisms isolated from rats or mice. By testing sera from healthy rats in 3 different colonies by use of immunofluorescence technique, antibodies were found in several sera.

Animals↗