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Biomedical subjects

O Magnusson

Publications and source records attributed to O Magnusson.

At least 55 records · Page 3Linked to original sources
PubMed1986

The effect of selective noradrenergic lesions upon the stimulation by noradrenaline of inositol phospholipid breakdown in rat hippocampal miniprisms.

The breakdown of inositol phospholipid (PI) stimulated by hippocampal noradrenaline in rat miniprisms in vitro was used as an index of alpha 1-adrenoceptor function after selective noradrenergic denervation. Selective denervation was produced by microinjections of 6-hydroxydopamine (6-OHDA) into either the dorsal noradrenergic bundle (DNAB) or the locus coeruleus (LC), or by systemic treatment with the noradrenergic neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine). Fourteen days after these treatments, there was a large depletion of cortical noradrenaline but no change in the stimulation of hippocampal PI breakdown by noradrenaline. It is concluded that selective noradrenergic denervation under the conditions used here does not lead to hippocampal alpha 1-adrenoceptor supersensitivity as assessed by noradrenaline-stimulated PI breakdown.

Animals↗
PubMed1986

The selective dopamine D2 receptor antagonist raclopride discriminates between dopamine-mediated motor functions.

The actions on central dopamine (DA) mechanisms of raclopride, a new substituted benzamide, were studied by means of behavioural and biochemical methods in the rat. Raclopride blocked the in vitro binding of the dopamine D2 antagonist 3H-spiperone (IC50 = 32 nM), but not of the unselective D1 antagonist 3H-flupenthixol (IC50 greater than 100,000 nM) in rat striatum, and failed to inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100,000 nM). Raclopride caused a dose-dependent increase in the DA metabolites HVA and DOPAC in the striatum and olfactory tubercle. Behavioural studies showed that raclopride discriminates between the motor behaviours induced by the DA agonist apomorphine. Thus, unlike haloperidol, raclopride blocked apomorphine-induced hyperactivity at considerably lower doses than those inhibiting oral stereotypies. Moreover, raclopride showed a high separation between the doses for blockade of apomorphine-induced hyperactivity and those inducing catalepsy in rats. Raclopride caused a dose-dependent blockade of the specific binding of 3H-spiperone and 3H-N-n-propylnorapomorphine (3H-NPA) in vivo at doses similar to those blocking the behavioural effects of apomorphine. The maximal blockade of 3H-spiperone binding in vivo was lower for raclopride than for haloperidol. Raclopride caused a greater inhibition of 3H-NPA than of 3H-spiperone in vivo binding in the striatum. It is suggested that the ability of raclopride to discriminate between different DA-mediated functions may be attributed to a preferential blockade of a subclass of functionally coupled dopamine D2 receptors in striatal as well as in extrastriatal brain regions in the rat.

Adenylyl Cyclases↗
PubMed1986

Dopamine D2 receptors and dopamine metabolism. Relationship between biochemical and behavioural effects of substituted benzamide drugs.

The effect of the substituted benzamide dopamine D2 receptor antagonists sulpiride, raclopride, FLA 966(-), FLA 988(-), eticlopride and remoxipride as well as the "classical" dopamine antagonists, haloperidol and chlorpromazine, on the concentrations of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the brain of the rat was investigated. All compounds increased the turnover of dopamine, as defined by increased concentrations of DOPAC and HVA (without change in the concentration of dopamine) in the striatum in a dose-dependent manner. The doses of the compounds producing increased turnover of dopamine in the striatum were in the same range as those displacing the in vivo binding of [3H]spiperone in the striatum. In addition, for all the compounds tested in the study, an increase in the turnover of dopamine to about 300% of control was observed for doses antagonising the stereotypy produced by the dopamine agonist, apomorphine. On the other hand, no consistent relationship between increased turnover of dopamine and the doses of the compounds required to antagonise apomorphine-induced hyperactivity was found. This result was also found in limbic areas. Remoxipride and haloperidol had little or no effect on the turnover of dopamine in either the hypothalamus or substantia nigra at the ED50 doses of these compounds for antagonism of apomorphine-induced stereotypy.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Forebrain serotonergic involvement in avoidance learning.

The one-way active avoidance deficit caused by the serotonergic (5-HT) releasing compound p-chloroamphetamine (PCA) was examined in rats after degeneration of 5-HT neurons in the forebrain. Injection of 5,7-dihydroxytryptamine (5,7-DHT) into the forebrain in desipramine (20 mg/kg)-pretreated rats resulted in a 65-70% decrease in 5-HT concentrations in the prefrontal cortex and hippocampus without any significant effect on striatal 5-HT. Slight reductions in noradrenaline (NA) (25%) and dopamine (DA) (34%) concentrations were observed in the prefrontal cortex only. The 5,7-DHT lesions markedly attenuated the impaired avoidance performance induced by PCA (2.5 mg/kg), suggesting that the avoidance deficit depends on intact 5-HT terminals in cortex and/or hippocampus. The 5,7-DHT lesion alone caused a slight but significant impairment of acquisition. The results suggest that 5-HT terminal systems in the forebrain play an important role in avoidance learning.

5,7-Dihydroxytryptamine↗
PubMed1985

Is inhibition of striatal synaptosomal tyrosine hydroxylation by dopamine agonists a measure of dopamine autoreceptor function?

Rat striatal synaptosomal tyrosine hydroxylation was inhibited dose- and pH dependently by a number of dopamine agonists. The catecholic agonists apomorphine and (-)N-n-propylnorapomorphine inhibited synaptosomal tyrosine hydroxylase completely, with IC50 values of around 0.3 mumol/l at pH 6.6. The noncatechol agonists pergolide and bromocriptine and the putative dopamine autoreceptor agonists 3-PPP(-), 3-PPP(+), HW-165 and B-HT 920 produced only partial inhibition of synaptosomal tyrosine hydroxylation at high concentrations. Comparison of the inhibition of synaptosomal and soluble tyrosine hydroxylase indicated that the inhibition produced by apomorphine could be ascribed to a direct effect on the enzyme, whereas this was not the case for the noncatechol agonists. The inhibition produced by pergolide and 3-PPP(-) was not antagonised by either dopamine receptor or alpha-adrenoceptor antagonists. The present results have been compared with results reported in the literature for inhibition of synaptosomal tyrosine hydroxylation and for two other tests of dopamine autoreceptor agonist activity (inhibition of dopamine release from striatal slices in vitro, and inhibition of the gamma-butyrolactone induced increase in dopamine synthesis in vivo). It is concluded that inhibition of striatal synaptosomal tyrosine hydroxylation by dopamine agonists does not fulfil the criteria required for it to be considered as a useful measure of dopamine autoreceptor function.

Adrenergic alpha-Agonists↗
PubMed1985

Increased total activity in the rat after L-tryptophan plus the monoamine oxidase-A inhibitor amiflamine but not after L-tryptophan plus clorgyline.

The effect of pretreatment with either saline or the monoamine oxidase-A inhibitors clorgyline and amiflamine upon the total activity, locomotion and rearing behaviour of the rat induced by various doses of the monoamine precursor L-tryptophan was studied by use of automated activity boxes. Amiflamine (2.5 and 5.0 mg kg-1, i.p.) increased in a dose-dependent manner total activity and to a lesser extent, locomotion when given 60 min before L-tryptophan (100 mg kg-1, i.p.). The increased activity was seen after amiflamine plus either 25 or 75 mg kg-1 L-tryptophan. Rearing behaviour was not affected. Analysis of 5-hydroxytryptamine (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) by high performance liquid chromatography with electrochemical detection indicated that in both frontal cortex and hypothalamus, amiflamine (at both doses) increased 5-HT and reduced 5-HIAA concentrations. Combination of amiflamine with L-tryptophan (100 mg kg-1, i.p.) resulted in a higher 5-HT concentration being found than after amiflamine alone. L-Tryptophan treatment alone did not change 5-HT concentrations but increased 5-HIAA concentrations. Clorgyline, at a dose of either 1 or 5 mg kg-1 i.p. plus L-tryptophan (25 or 100 mg kg-1, i.p.) did not increase total activity, locomotion or behaviour. A number of possible explanations for the differences in the behavioural effects of clorgyline and amiflamine when given with L-tryptophan are discussed. It is concluded that in addition to monoamine oxidase-A inhibition, other pharmacological effects of the drugs, such as 5-HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L-tryptophan.

Animals↗
PubMed1985

[Selective antidopaminergic properties of remoxiprid, a new potential antipsychotic agent].

The pharmacology of S-(-)-3-bromo-2, 6-dimethoxy-N-(1-ethyl-2-pyrrolidinylone-ethyl)-benzamide (remoxipride), a new neuroleptic compound belonging to the benzamide group, has been thoroughly investigated using a number of different techniques. The compound blocks apomorphine-induced stereotypies and hyperactivity, indicating potent antidopaminergic activity. However, in contrast to many other antidopaminergic compounds, remoxipride induces only weak and atypical catalepsy, which indicates that remoxipride might exert less antidopaminergic side effects than other neuroleptic drugs. In vivo receptor binding studies using 3H-spiperone show that remoxipride preferentially blocks dopamine receptors only are blocked to 60% even at very high doses. In vitro receptor binding studies show that remoxipride is devoid of affinity for receptors other than the dopamine D2 receptors except at higher concentrations. These results indicate that remoxipride should be a clinically effective neuroleptic compound exerting less extrapyramidal side effects than the neuroleptics currently used.

Animals↗
PubMed1984

Remoxipride, a new potential antipsychotic compound with selective antidopaminergic actions in the rat brain.

The novel substituted benzamide, remoxipride, preferentially blocked apomorphine-induced hyperactivity with weak effects on stereotypies. The potency of remoxipride was about 50 times higher than that of sulpiride. Remoxipride caused a weak, atypical form of catalepsy and showed a high separation between the ED50 for blockade of apomorphine-induced hyperactivity and the ED50 for induction of catalepsy (ratio 24). Remoxipride was shown to be a selective dopamine D2 receptor antagonist since it displaced [3H]spiperone (IC50 = 1570 nM) but not [3H]flupentixol (IC50 greater than 100 000 nM) in rat striatum, and did not inhibit striatal DA-sensitive adenylate cyclase in vitro (IC50 greater than 100 000 nM). Remoxipride is a potent antagonist of D2 receptors showing a dose-dependent blockade of [3H]spiperone and [3H]n-propylnorapomorphine in vivo binding with a potency equal to that of chlorpromazine. In contrast to haloperidol, remoxipride caused a preferential blockade of in vivo [3H]spierone binding in the mesolimbic DA rich areas and the substantia nigra with much less effect in the striatum. In addition, remoxipride produced a preferential increase of DA utilization following synthesis inhibition in the olfactory tubercle. Only minor changes in NA and 5-HT metabolism were observed while HVA and DOPAC levels were markedly elevated. Taken together, these results indicate that remoxipride is a potent, selective D2 receptor blocking agent with a preferential action in mesolimbic and extrastriatal dopamine-containing neurons.

Adenylyl Cyclases↗
PubMed1984

Retention deficits induced by acute p-chloroamphetamine following fear conditioning in the rat.

Rats were given four inescapable shocks (1.0 mA) when confined to the right-hand corner of a modified shuttlebox. p-Chloroamphetamine (PCA) injected just before the retention test 24 h later completely blocked the immobile posture that was observed after saline injections. This retention deficit was shown to be selectively associated with 5-hydroxytryptamine (5-HT) release, since the administration of the 5-HT uptake inhibitors zimelidine and citalopram 60 min prior to PCA antagonized this effect. The 5-HT specificity of the deficit was further established by the findings that 5-HT-depleted rats (PCA, 2 x 10 mg/kg, and fenfluramine, 2 x 25 mg/kg), but not NA-depleted rats (DSP4, 1 x 50 mg/kg), or rats treated with zimelidine (2 x 20 mg/kg) 60 min before PCA (2 x 10 mg/kg), showed an almost complete blockade of the retention failure. The data presented may provide a useful experimental model for investigating the efficacy of functional 5-HT activity in the treatment of phobic anxiety.

Amphetamines↗
PubMed1984

Stereoselective inhibition of monoamine oxidase and semicarbazide-sensitive amine oxidase by 4-dimethylamino-2,alpha-dimethylphenethylamine (FLA 336).

The in vitro inhibition by amiflamine [FLA 336(+)] and related compounds of the activity of rat monoamine oxidase (MAO) -A and -B, rat semicarbazide sensitive amine oxidase (SSAO) and human platelet poor plasma benzylamine oxidase was studied. Amiflamine was an MAO-A selective inhibitor, but also inhibits SSAO with both a reversible (competitive, Ki = 200 mumol/l) and a small time-dependent component which was irreversible in nature. The optical isomer FLA 336(-) was ten times less potent towards MAO-A. However, this compound was much more potent an inhibitor of SSAO (competitive, Ki = 4.6 mumol/l). The amiflamine metabolites FLA 788(+) and FLA 668(+) inhibited SSAO, but only at concentrations considerably higher than required for MAO-A inhibition. Ex vivo experiments indicated that there was no significant irreversible inhibition of rat heart and lung SSAO after both single and repeated administration of amiflamine at doses up to 20 times higher than required for inhibition of MAO-A within central serotoninergic neurones.

Amine Oxidase (Copper-Containing)↗
PubMed1984

Behavioral and biochemical effects of subchronic treatment with (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine in the rat: dopamine receptor sensitivity and tolerance.

Male Sprague-Dawley rats were treated for 3 weeks with (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP). Twenty-four hours, but not 72 hours, after withdrawal of the treatment there was an increase in locomotor activity in comparison with saline treated controls. At the same time there was a decrease in striatal DOPAC and HVA and an increased locomotor activity response to apomorphine, indicating supersensitive dopamine receptors. There was no evidence for behavioral tolerance since the suppression of locomotor activity after an acute dose of (-)3-PPP was the same in (-)3-PPP-pretreated as in saline-treated controls. Plasma levels of (-)3-PPP in these animals were, however, slightly decreased.

Animals↗
PubMed1984

Comparison of an elemental and two polymeric diets in colectomized patients with or without intestinal resection.

The absorption of nutrients and minerals from the small bowel on enteral diets of different composition has been studied in seven ileostomy patients without or with only minor (< 100 cm) distal small bowel resection (group A) and in nine patients with major (> 100 cm) resections, i.e. jejunostomies (group B). In group A, a moderate-fat polymeric diet (MF) was compared to a peptide-based low-fat elemental diet (PD). Nitrogen and potassium absorption was higher on the MF, while the absorption of other nutrients and minerals studied did not differ. In group B a low-fat polymeric diet (LF) was also tested. Jejunostomy volumes were higher on the PD diet compared to the polymeric diets, as were losses of sodium and potassium. Nitrogen absorption was lower on the PD diet. Comparison of the MF and LF polymeric diets showed equal energy losses, while jejunostomy volumes and sodium losses were higher on the MF diet. Calcium absorption was higher and balance better on the LF diet. We conclude, that (a) elemental diets offer no nutritional advantages in enteral feeding of patients with intact or impaired small bowel function, and (b) we suggest that a low-fat polymeric diet could replace elemental diets in patients with malabsorption.

Journal Article↗
PubMed1984

Intra- and extraneuronal monoamine oxidase.

By use of monoamine reuptake inhibitors, it is possible to study the intra- and extraneuronal components of monoamine deamination in brain. In both man and rat, the ratios of activities of MAO-A/MAO-B are higher intra- than extraneuronally . As a result of this difference in cellular localisation in the brain, loss of neurones produces a change in the ratios of activities of MAO-A/MAO-B. It is also possible selectively to inhibit the activity of MAO-A within a given neurone population. The alpha-methyl substituted monoamine amiflamine has been shown to inhibit MAO-A within serotoninergic neurones at lower doses than are required for inhibition in other neurones. The usefulness of this compound in the elucidation of the functions of intra- and extraneuronal MAO are discussed.

Animals↗
PubMed1983

Concentrations of 5-hydroxyindoleacetic acid and homovanillic acid in the cerebrospinal fluid of chronic therapy-resistant schizophrenics before and after hemodialysis therapy.

The concentrations of the monoamine metabolites 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) have been determined by high-performance liquid chromatography in samples of lumbar cerebrospinal fluid from chronic therapy-resistant schizophrenics, both before and after either inactive or active hemodialysis for 10 weeks. A reasonable test-retest reliability was found for 5-HIAA during the inactive dialysis, but this was not found during active dialysis.

Adult↗
PubMed1980

Simultaneous determination of dopamine, DOPAC and homovanillic acid. Direct injection of supernatants from brain tissue homogenates in a liquid chromatography--electrochemical detection system.

A simple method based on high-performance liquid column chromatography with electro-chemical detection is described for the simultaneous determination of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in discrete brain regions of rats. The supernatant of a tissue homogenate is injected directly onto a liquid chromatograph, thus omitting the commonly adopted adsorption step. Of the four different supports tested Nucleosil C15 (5 micron) was found superior with respect to chromatographic performance. The effects of pH, methanol and the ion-pairing agent hexyl sulfate on the retention were studied. The mobile phase used in the final studies consisted of citrate buffer pH 4.25-methanol (92:8, v/v) containing hexyl sulfate (1.7 . 10(-3) M). Standard curves of dopamine, DOPAC and HVA were found linear up to about 600 pmol per injection for each compound. The precisions of the chromatographic step were (Srel. %): 0.72% (dopamine), 1.26% (DOPAC) and 2.69% (HVA).

3,4-Dihydroxyphenylacetic Acid↗
PubMed1980

Early complications after surgical treatment for Crohn's disease with particular reference to factors affecting their development.

Early postoperative mortality and morbidity and factors that might be of importance in this respect were studied in a series of consecutive patients resected for classical Crohn's disease (IPI) or mainly colonic disease (CPC). The operative mortality was comparatively low after surgery for both primary and recurrent disease (1.5 and 2.0% respectively). The complication rate was marked, particularly so after primary surgery for colonic disease. Weight loss, abnormally low serum albumin or TIBC referred to as nutritional markers, appeared to have no predictive value in determining patients at risk for postoperative complications. Steroid treatment prior to operation was not associated with increased postoperative complication rate. The important factor influencing postoperative complication rate was the occurrence of preoperative septic complications and surgery performed for urgency was associated with an increased complication rate only when associated with pre-existing septic complications. The observations would appear to speak in favour of surgery at an earlier stage in patients with Crohn's disease who do not respond to medical treatment.

Crohn Disease↗