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Biomedical subjects

A Carlsson

Publications and source records attributed to A Carlsson.

At least 307 records · Page 17Linked to original sources
PubMed1982

Monophenolic octahydrobenzo[f]quinolines: central dopamine- and serotonin-receptor stimulating activity.

Eight monophenolic cis- and trans-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolines have been synthesized and tested for central dopamine- and serotonin-receptor stimulating activity, using biochemical and behavioral tests in rats. The trans-7-, -8-, and -9-hydroxy isomers all elicited central pre- and postsynaptic dopaminergic receptor stimulation, while the trans-10-hydroxy isomer was devoid of dopaminergic activity but instead showed central serotoninergic activity. In all four isomeric pairs, the trans isomers were consistently much more potent than their corresponding cis analogues. The apparent presynaptic selectivity of the dopaminergic cis isomer cis-9-hydroxy-4-n-propyl-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinoline could not be confirmed due to the toxic properties of this compound. Central dopamine receptors (autoreceptors and postsynaptic receptors) can accept dopaminergic compounds with one of possibly two N-substituents being larger than n-propyl, if this substituent is properly oriented in relation to the rest of the molecule.

5-Hydroxytryptophan↗
PubMed1982

Brain monoamine abnormalities in the two types of Creutzfeldt-Jakob disease.

Analysis of monoamine concentrations in brain tissue was carried out on the two types of Creutzfeldt-Jakob disease (CJD). The results showed decreased levels of catecholamines compared to control cases in a number of areas, and the reductions were most pronounced for dopamine. In general, the case classified as the amyotrophic form of CJD showed a greater degree of a monoamine loss than the case with spongiform encephalopathy, which is the typical transmissible form of CJD. These findings support the scarce available data indicating disturbances in the catecholaminergic systems in these types of brain diseases, and may have therapeutic implications.

Aged↗
PubMed1982

Effect of diazepam on cerebral monoamine synthesis during hypoxia and hypercapnia in the rat.

In view of the fact that diazepam has been shown to prevent an increase in catecholamine synthesis and/or turnover rates in stressful situations, and to modify the cerebral metabolic (and circulatory) response to hypoxia and hypercapnia, the influence of the drug on synthesis rates of DOPA and 5-HTP in three regions of the rat brain were studied under normoxic-normocapnic conditions, as well as in hypoxia and hypercapnia. In order to exclude a modifying influence of variations in tissue pO2 during hypercapnia, cerebral venous pO2 was kept at control values by moderate arterial hypoxia. When compared to the control state (paralyzed animals maintained on 70% N2O) normoxic and normocapnic animals given diazepam (in the absence of N2O) showed a slightly enhanced DOPA synthesis in limbic structures and reduced 5-HTP synthesis in limbic structures and striatum. In hypoxia, the drug considerably curtailed DOPA synthesis in limbic structures and striatum but had no effect on synthesis rate in cortex. The drug also appeared to exaggerate the generalized reduction in 5-HTP synthesis observed under 70% N2O. In hypercapnia, diazepam reduced the enhanced rate of DOPA synthesis (observed under 70% N2O) in striatum but left that in the cortex unchanged. The drug prevented the hypercapnia-induced increase in 5-HTP synthesis, observed under 70% N2O. It is concluded that diazepam significantly alters dopamine and serotonin synthesis in hypoxia and hypercapnia. Probably an indirect action, perhaps related to the stress-alleviating effect of diazepam, is involved. The results suggest that the effect of the drug on cerebral metabolic rate and blood flow in hypoxia and hypercapnia is unrelated to changes in noradrenaline synthesis or turnover. Furthermore, although the results demonstrate that diazepam modulates dopamine metabolism in hypoxia and hypercapnia it seems questionable that this influence can explain the metabolic and circulatory effects of diazepam in these conditions.

5-Hydroxytryptophan↗
PubMed1982

Exposure to toluene: concentration in subcutaneous adipose tissue.

Twelve male subjects were exposed to a toluene concentration of about 300 mg/m3 in the inspiratory air during rest and/or physical exercise on a bicycle ergometer. Each subject was exposed during four 30-min periods. Before exposure the subjects' body fat was calculated by means of underwater weighing and skeletal measurements. Needle biopsies of subcutaneous adipose tissue were taken up to 12 d after the exposure was concluded. The concentration of toluene in the adipose tissue was determined by gas chromatography after evaporation into nitrogen at a high temperature. After exposure at rest for 2 h, the mean concentration of toluene in adipose tissue was 0.7 mg (7.7 mumol)/kg. The corresponding value after 2 h of work at 50 W was 9.9 mg (109 mumol)/kg. There was a declining concentration of toluene in adipose tissue with an increasing degree of obesity. The half-time for toluene in adipose tissue ranged between 0.5 and 2.7 d. It increased with increasing amounts of body fat.

Adipose Tissue↗
PubMed1982

Exposure to toluene: uptake, distribution and elimination in man.

Twelve male subjects were exposed to a toluene concentration of about 300 mg/m3 in the inspiratory air during rest and/or physical exercise on a bicycle ergometer. Each subject was exposed during four consecutive 30-min periods. The uptake of toluene was about 50% of the inspired amount at rest, with a decrease to about 30% at a work load of 150 W during the fourth period. The total uptake of toluene during 2 h of work at 50 W was about 2.4 times higher than at rest. There was a close linear correlation between the alveolar and arterial concentrations of toluene, both during and after exposure. The means of the exhaled amounts of unchanged toluene during the first 20 h after exposure ranged between 7 and 14% of the amount taken up. The urinary excretion of hippuric acid indicated an influence of food, especially at low uptake levels.

Adult↗
PubMed1981

Effects of pentobarbital and diazepam on rat plasma amino acid patterns.

Intraperitoneal injections with pentobarbital and diazepam caused an increase in the concentration of most plasma amino acids in rat. In contrast, tryptophan was significantly decreased after treatment with pentobarbital. The tyrosine level showed no change and was thus actually reduced after pentobarbital treatment in relation to the total pool of large neutral amino acids. The possibility should be considered that these changes in plasma amino acid patterns may lead to reduced transport of e.g. tryptophan and tyrosine into the brain, which in turn might retard the synthesis of monoaminergic neurotransmitters. The transport and action of several aromatic amino acids used as therapeutic agents may also be influenced.

Amino Acids↗
PubMed1981

Effects of hypophysectomy, adrenalectomy and (-)-propranolol on ethanol-induced decrease in plasma amino acids.

In previous studies we have demonstrated that an acute dose of ethanol cause an immediate decrease in most plasma amino acids in both man and rat. This effect of ethanol is partly inhibited by the beta-adrenergic antagonist (-)-propranolol, partly by adrenalectomy or hypophysectomy and almost completely by a combination of adrenalectomy with (-)-propranolol. This finding suggests an involvement of both beta-adrenergic mechanisms and steroids from the adrenal cortex in the ethanol-induced decrease in plasma amino acids.

Adrenalectomy↗
PubMed1981

The activities of monoamine oxidase-A and -B, succinate dehydrogenase and acid phosphatase in the rat brain after hemitransection.

The activities of monoamine oxidase-A and -B were determined in four brain regions (limbic system, occipito-temporal cortex, hemispheres and striatum) of the rat 0, 3, 6, 9 and 14 days after hemitransection of the left side. No larger or consistent change in the activity of monoamine oxidase-A towards 5-hydroxytryptamine was found for the left (hemitransected) side with respect to the right side for any of the rats. The monoamine oxidase-B activity towards beta-phenethylamine increased in the left side striatum to a significant level by 3 days, and in the hemispheres and occipito-temporal cortex on the left side, with respect to the right side by 9 days, but no significant changes were found for the limbic system. A small decrease in the activity of succinate dehydrogenase was found in the striatum on the left side by 9 days after hemitransection, but no change in the activity of acid phosphatase was found in this brain region.

Acid Phosphatase↗
PubMed1981

Monoamine oxidase-A and -B activities in the brain stem of schizophrenics and non-schizophrenic psychotics.

In the pons of autopsy cases who had suffered from chronic schizophrenic or nonschizophrenic psychoses, an increased activity of monoamine oxidase -B but not -A was found, as compared with age-matched controls. Consequently, the ratio of the activities of MAO-B : MAO-A was elevated in the cases of psychosis. There was no significant difference in enzyme activities between schizophrenic and nonschizophrenic psychoses. Lobotomy appeared not to influence the monoamine oxidase activity. Increased ratios of the activities of MAO-B : MAO-A in various brain parts of chronic schizophrenics in comparison with age-matched controls was found in the previously published data of Eckert et al (1980) and Schwartz et al. (1974) but not Crow et al. (1979). The mechanism underlying the change in enzyme activities is unclear. There seems to exist an association between an increased monoamine oxidase-B activity and degenerative processes in the brain resulting in loss of neuronal activity. The change observed may be linked either to pathological processes associated with chronic psychosis or to long-term treatment with neuroleptic drugs.

Adult↗
PubMed1981

Effects of a new type of 5-HT receptor agonist on male rat sexual behavior.

8-Methoxy-2-(di-n-propylamino) tetralin (8-OMe-DPAT) and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) are two new drugs exerting selective actions on brain 5-HT neurotransmission. In the present experiments we have investigated the effects of these two drugs on male rat sexual behavior. It was found that both drugs reduce the number of intromissions preceding ejaculation and shorten the ejaculation latency. These effects are extremely pronounced and several animals ejaculate at the first intromission. In addition 8-OH-DPAT produced a slight reduction of the post-ejaculatory interval. There were no significant effects on latency to initiate copulation or in the number of mounts preceding ejaculation. Finally, sexual behavior was partly or completely restored in castrated male rats after injection with 8-OMe-DPAT or 8-OH-DPAT.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1981

Monophenolic 2-(dipropylamino)indans and related compounds: central dopamine-receptor stimulating activity.

Monophenolic (2-(dipropylamino)indans and related compounds have been synthesized and tested for central dopamine-receptor stimulating activity, using biochemical and behavioral tests in rats and emesis tests in dogs. The active compounds possess similar relative potencies in eliciting the three different dopamine-receptor mediated effects measured. 4-Hydroxy-2-(dipropylamino)indan was the most potent of the new compounds. The corresponding 5-hydroxy analogue was less active. 4-Hydroxy-2-[(dipropylamino)methyl]indan is a new type of dopaminergic agent with a phenylpropylamine moiety in its framework instead of the phenylethylamine structure, common to most dopamine-receptor agonists. This compound was 10-20 times less active than apomorphine. 6,7,8,9-Tetrahydro-1-hydroxy-N,N-dipropyl-5H-6-benzocycloheptenylamine and 5-hydroxy-2-[(dipropylamino)methyl]tetralin were both inactive. Since the intramolecular distances between functional groups in the indans studied here are different from those in, for example, apomorphine, it is concluded that a certain variation of these distances can be accepted by the receptor. It could also be demonstrated that the position of the OH group on the aromatic ring is of importance for the activity and that emetic activity may be associated with dopaminergic agonists of the indan as well as of the tetralin type of structure.

Animals↗
PubMed1981

3-Phenylpiperidines. Central dopamine-autoreceptor stimulating activity.

Thirty compounds related to the selective dopamine-autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine have been synthesized and tested for central dopamine-autoreceptor stimulating activity. The 3-(3-hydroxyphenyl)piperidine moiety seems indispensable for high potency and selectivity. Introduction of an additional hydroxyl group into the 4 position of the aromatic ring gives a compound with dopaminergic activity but lacking selectivity for autoreceptors. 3-(3-Hydroxyphenyl)-N-n-propylpyrrolidine, 3-(3-hydroxy)-N-n-propylperhydroazepine, and 3-(3-hydroxyphenyl)quinuclidine were all inactive. The most potent compounds were the N-isopropyl-, N-n-butyl-, N-n-pentyl-, and N-phenethyl-substituted 3-(3-hydroxyphenyl)piperidine derivatives. None of the compounds investigated seemed to have central noradrenaline- or serotonin-receptor stimulating activity.

5-Hydroxytryptophan↗
PubMed1981

Some current problems related to the mode of action of antidepressant drugs.

An important relationship between antidepressant drugs and the monoamine transmitters of the brain is generally recognized. Major groups of established antidepressants are inhibitors of monoamine inactivation (by reuptake or monoamine oxidase) or monoamine precursors. However, the tricyclic antidepressants have many actions in addition to the blockade of monoamine reuptake, e.g. blockade of muscarinic, alpha-adrenergic and histaminic receptors and general membrane effects which may lead to cardiotoxicity. The discovery that certain antihistaminic agents devoid of condensed ring systems are fairly potent inhibitors of monoamine reuptake led to the synthesis of zimelidine, a potent and selective 5-HT reuptake inhibitor with little affinity for receptors and almost devoid of cardiotoxicity. Careful pharmacological studies and clinical trials with such selective monoaminergic agents are of considerable value for testing the possible role of monoaminergic mechanisms in various aspects of human and animal behaviour and for central nervous disorders, including depression.

Antidepressive Agents↗