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Biomedical subjects

A Carlsson

Publications and source records attributed to A Carlsson.

At least 19 recordsLinked to original sources
PubMed1992

6-Hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine and analogs: new centrally acting 5-HT1A receptor agonists.

The ring-closed phenylethylamine analogue 6-hydroxy-3-n-propyl-2,3,4,5-tetrahydro-1H-3-benzazepine (1) is a 5-HT1A receptor agonist of moderate potency, according to both in vivo biochemical data and in vitro binding data. The active compounds of this series also induce the 5-HT behavioral syndrome. Molecular modeling studies were performed with molecular mechanics calculations, and a tentative explanation for the relatively low potency of these serotonergic benzazepines is provided.

Animals↗
PubMed1992

Antagonism of cocaine's pharmacological effects by the stimulant dopaminergic antagonists, (+)-AJ76 and (+)-UH232.

The aminotetralins (+)-AJ76 and (+)-UH232 are stimulant dopaminergic antagonists, which may preferentially antagonize autoreceptors of dopamine nerve terminals. Both agents antagonized cocaine's depressant effects on firing rates of ventral tegmental dopaminergic neurons, but (+)-UH232 was much more potent. When injected simultaneously with cocaine, (+)-UH232 inhibited and (+)-AJ76 enhanced the locomotor stimulation observed during the first 30 min following s.c. cocaine administration. However, (+)-AJ76 antagonized cocaine-induced stereotypies as well as the later more intense cocaine locomotor stimulation. It is suggested that preferential dopamine autoreceptor antagonists may provide a novel approach to a pharmacotherapy for treating cocaine abuse.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Pharmacologic properties of (-)-3PPP (preclamol) in man.

The dopamine (DA) autoreceptor agonist (-)-3PPP (preclamol) was tested in male schizophrenic volunteers for safety. The drug was administered intramuscularly in a single rising dose design, crossed with a similar "rising dose" placebo period; all evaluations and raters were blind to drug or placebo administration. Pharmacokinetic, endocrine, safety, and mental status outcome measures were completed before and after each single dose of drug or placebo. Pharmacokinetic analysis showed blood levels between 200-500 pmoles/ml after the intramuscular drug doses of 30-40 mg. Drug half life is 2-2.5 hrs. Growth hormone (GH) levels were elevated in a linear fashion to the 30 mg dose; whereafter, the drug failed to affect GH at all. All safety evaluations were negative, including any untoward effects on the major organ systems. After single dose drug administration, evidence of antipsychotic action occurred in two of the four subjects. This study suggests that (-)-3PPP/preclamol is a safe drug for study in the treatment of schizophrenia and may have antipsychotic efficacy.

Administration, Oral↗
PubMed1992

Interaction between glutamatergic and dopaminergic tone in the nucleus accumbens of mice: evidence for a dual glutamatergic function with respect to psychomotor control.

The rotation induced by a unilateral injection of the competitive NMDA receptor antagonist AP-5 was studied in mice with different tone in the central dopaminergic systems. AP-5 induced contralateral rotation in monoamine-depleted mice and in monoamine-depleted mice treated with a dopamine D-1 receptor agonist. In contrast, AP-5 induced predominantly ipsilateral rotation in monoamine-depleted mice treated with a mixed D-1/D-2 or a D-2 selective dopamine agonist and in mice with intact monoaminergic systems.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Differential locomotor interactions between dopamine D1/D2 receptor agonists and the NMDA antagonist dizocilpine in monoamine-depleted mice.

Previous work in our laboratory has shown that the non-competitive N-methyl-D-aspartate antagonist dizocilipine (MK-801) interacts synergistically with the mixed dopamine (DA) receptor agonist apomorphine and the DA D 1 agonist SKF 38393 to promote locomotion in monoamine-depleted mice. The purpose of the present study was to compare the roles of DA D 1 and DA D 2 receptors in this interaction. To that end, dizocilpine was given in combination with either the DA D 1 receptor agonist SKF 38393 or the selective DA D 2 receptor agonist quinpirole or the preferential DA D 2 agonist bromocriptine. In general, the locomotor stimulatory effects produced by SKF 38393 were potentiated by dizocilpine, whereas the locomotor stimulation produced by quinpirole and bromocriptine was counteracted. However, baseline activity, which partly depends on how much time is allowed to elapse between administration of the DA agonist and commencement of locomotor recording, and partly on the dose of the DA agonist, seems to be an important factor that determines whether dizocilpine will have a weakening or a potentiating effect. Interestingly, the competitive NMDA antagonist D-CPPene displayed a different pattern of interaction with SKF 38393 and quinpirole in that synergistic effects were observed with both DA agonists, most conspicuously so with the DA D 2 receptor agonist. The results are interpreted in the light of present knowledge of basal ganglia neuroanatomy; they are discussed in relation to the "direct" and "indirect" pathways from the striatum to the thalamus, proposed to form part of positive and negative cortico-striato-thalamo-cortical loops, respectively, as well as to the presumed presynaptic D 2 receptors on corticostriatal glutamatergic neurons.

Animals↗
PubMed1992

Immunoglobulins, lysozyme and lactoferrin in the teat and udder of the dry cow during endotoxin-induced inflammation.

Immunoglobulins (Ig) and antibacterial proteins like lysozyme and lactoferrin are components of the humoral defence against infections. Changes in Ig, lysozyme and lactoferrin concentrations during endotoxin-induced inflammation in the test cistern and udder quarter of the dry cow were studied. Surgical closure of the passage between teat and udder cisterns enabled studies of reactions in the teat cistern without interference of the mammary gland. After endotoxin infusion, IgG1, IgG2, lysozyme, and to some extent IgM, increased in the teats and udder quarters, and were positively correlated with changes in somatic cell counts. No significant changes were observed in IgA or lactoferrin. The origin and significance of Ig, lysozyme and lactoferrin in the bovine teat and udder are discussed. Ig probably originated both from serum and from local plasma cells, while leukocytes appeared to be the source of lysozyme during inflammation. Secretory epithelium appeared to be the source of lactoferrin. Support for this theory was the almost total absence of lactoferrin in teat cistern samples.

Animals↗
PubMed1992

Pit and fissure sealing and mutans streptococci levels in saliva.

The effect of preventive pit and fissure sealants with a resin-based material on the number of salivary mutans streptococci was evaluated in 46 healthy 12-year-old school children (F group) with medium or high counts during a 1-year study period. As controls served 33 children of the same age with the same bacterial levels at baseline (C group) and 55 children with low levels (L group). Caries prevalence and incidence were registered clinically and radiographically. Sealing of all accessible pit and fissures was carried out in the F group with a light-cured Bis-GMA sealant. Bacterial levels at baseline and 3, 6, 12 and 52 weeks after treatment were estimated with a chairside method. The results disclosed a significant (P < 0.05) drop in the number of salivary mutans streptococci in the F and C groups at all sampling occasions compared to baseline. There were however no differences between the groups during the study period. Both the caries prevalence and incidence were significantly (P < 0.05) higher in F and C groups when compared to the L group. The results suggest that preventive pit and fissure sealing with a resin based material does not affect salivary mutans streptococci levels.

Child↗
PubMed1991

Effects of repeated administration of the preferential dopamine autoreceptor antagonist, (+)-AJ76, on locomotor activity and brain DA metabolism in the rat.

AJ76, the cis-(+)-(1S,2R) enantiomer of 5-methoxy-1-methyl-2-(n-propyl-amino) tetralin is a dopamine autoreceptor antagonist which has shown locomotor stimulatory properties, especially in habituated rats. AJ76 was given repeatedly to male rats at different time intervals and different doses to investigate if tachyphylaxis/tolerance would develop. Tolerance did not occur if AJ76 (300 mumol/kg p.o.) was administered once daily for 7 days, (regarding both stimulation of locomotor activity and increase in brain DOPAC levels). Tolerance occurred after a single dose of 52 mumol/kg s.c. given in the morning followed by the same challenge dose 4 but not 24 h later. When the first dose was decreased to 13 mumol/kg s.c. no tachyphylaxis could be demonstrated regarding stimulation of locomotor activity. It is concluded that AJ76 induces a dose-dependent and short lasting tachyphylaxis, while no tolerance is observed after one week repeated administration. The possible mechanism behind these effects are discussed.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effects of the partial dopamine receptor agonists SDZ 208-911, SDZ 208-912 and terguride on central monoamine receptors. A behavioral, biochemical and electrophysiological study.

The partial dopamine receptor agonists SDZ 208-911 (N-[(8-alpha)-2,6-dimethylergoline-8-yl]-2,2-dimethylpropanamid e), SDZ 208-912 (N-[8-alpha)-2-chloro-6-methylergoline-8-yl]-2,2- dimethylpropanamide) and terguride (transdihydrolisuride; TDHL) were tested in biochemical, behavioral (locomotor activity) and electrophysiological assays in male rats. In reserpine-pretreated rats, SDZ 208-911 and terguride dose-dependently reduced striatal DOPA formation (NSD 1015 treatment) with similar efficacy (-80%) and potency as the selective D2 receptor agonist quinpirole (LY 171555). SDZ 208-912 only produced a partial reduction (-32%) at the highest dose tested. SDZ 208-911 and terguride partially reversed (by approximately 50%) the gamma-butyrolactone (GBL)-induced increase in striatal DOPA accumulation. Quinpirole produced a 100% reversal while SDZ208-912, per se, was inactive. While quinpirole decreased DOPA accumulation, all three partial agonists elevated striatal DOPA accumulation in non-pretreated rats with SDZ 208-912 being as potent and efficacious as haloperidol. The three partial agonists displayed comparatively high affinities in vitro for the dopamine D2 (3H-spiperone) receptor site and somewhat lower affinity for the 5-HT1A (3H-8-OH-DPAT) receptor site. SDZ 208-911 and SDZ 208-912 also showed high affinities for central alpha 2 (3H-idazoxane) receptors. In line with these findings, the partial ergoline agonists dose-dependently elevated the DOPA accumulation in the noradrenaline-rich cortical brain region and decreased the 5-HT synthesis rate (5-HTP accumulation) in the limbic brain region. Furthermore, high doses of SDZ 208-911 and terguride produced weak signs of the 5-HT behavioral syndrome (flat body posture) in reserpinized rats. In the locomotor activity studies in non-pretreated rats, SDZ 208-911, SDZ 208-912 and terguride reduced the activity to 10-20% of controls with SDZ 208-912 being approximately ten times less potent than the other two compounds. Weak postsynaptic dopamine receptor agonist effects of the partial agonists were demonstrated only in reserpine-pretreated rats; all three partial agonists tested produced occasional forward locomotion and the so-called "jerking" behavior. Extracellular single unit recordings were carried out in chloral hydrate-anesthetized rats to investigate the effects on firing rates of dopamine neurons located in the substantia nigra pars compacta. Intravenous administration of SDZ 208-911 and terguride depressed the firing rate by 42 and 53%, respectively, while apomorphine completely inhibited the cells. SDZ 208-912 only reduced the firing by 16% and some cells displayed a biphasic response with a weak depression at low doses that disappeared at high doses.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Butyrolactone↗
PubMed1991

Synergistic interactions between muscarinic antagonists, adrenergic agonists and NMDA antagonists with respect to locomotor stimulatory effects in monoamine-depleted mice.

The purpose of the present investigation was to study the effects of simultaneous manipulations of central cholinergic, adrenergic and glutamatergic systems on locomotion in an animal model of Parkinson's disease. Mice were deprived of their monoamine stores by pretreatment with the monoamine depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine, given 18 h and 60 min, respectively, before the acute experiment. Traditionally, only dopaminergic agonists have been shown to reverse the akinesia thus produced. However, in the present study it is demonstrated that if a muscarine receptor antagonist (atropine or biperiden) is combined with an alpha-adrenergic agonist/alpha-adrenergic agonist precursor (clonidine or L-alpha-methyl-dopa), a marked locomotor stimulation can be achieved, although either agent given alone is ineffective. Adding an NMDA antagonist (MK-801, ketamine or SDZ EAA 494) to the combination biperiden + clonidine resulted in further potentiation of the locomotor stimulatory effects.

Adrenergic alpha-Agonists↗
PubMed1991

Synergistic interactions between the NMDA antagonist dizocilpine and the preferential dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 with regard to locomotor stimulation in monoamine-depleted mice.

When administered to mice pretreated with the monoamine-depleter reserpine and the catecholamine synthesis inhibitor alpha-methyl-para-tyrosine, the preferential autoreceptor antagonists (+)-AJ76 and (+)-UH 232 induced weak locomotor stimulation. When either (+)-AJ 76 or (+)-UH 232 was combined with a subthreshold dose of the selective NMDA antagonist dizocilpine (MK-801), a marked locomotor stimulation was produced in monoamine-depleted mice. The mechanism of this stimulation, although reduced by dopamine antagonists, remains to be clarified.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Dopamine receptors, controlling dopamine levels in rat adrenal glands-comparison with central dopaminergic autoreceptors.

Previous work in this laboratory, as well as observations reported in the literature, indicate that the adrenal medulla contains dopamine (DA) receptors of the D-2 subtype, which among other things are capable of controlling the DA level in rat adrenal glands. To further characterize the DA receptors involved in the control of the adrenal DA level, the effects of 9 DA receptor agonists with various intrinsic activities were compared. After various periods of drug administration the rats were killed by decapitation and the DA content of the adrenal glands and the DOPAC content of the forebrain were measured by high-performance liquid chromatography with electrochemical detection. All the investigated DA receptors agonists caused an increase in adrenal DA level, although statistical significance was not reached in one case [(-)-HW 165]. Domperidone, a DA D-2 receptor antagonist which does not readily cross the blood brain barrier, blocked the DA-elevating effects of apomorphine, quinpirole, B-HT 920 and both enantiomers of 3-PPP. For the two ergolines terguride and SDZ 208-920 the blockade by domperidone was not complete, suggesting that their effects are mediated not only through DA, but also through other receptor systems. The dose of domperidone used (3 mg/kg) had but a marginal influence on brain DOPAC levels, supporting the almost exclusively peripheral effect of this agent. Our data indicate that the DA D-2 receptors which control the DA level in the adrenal medulla in rats, have characteristics similar to, though not identical with the autoreceptors in the forebrain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Effects of inhibition of monoamine oxidase on the levels of 5-S-cysteinyl adducts of catechols in dopaminergic regions of the brain of the guinea pig.

The occurrence of 5-S-cysteinyl adducts of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylalanine (DOPA) in brain tissue, appears to reflect in vivo autoxidation of DA, DOPA and DOPAC, respectively. In the striatum and in the limbic system of guinea pig, the levels of DOPAC and 5-S-cysteinyl-DOPAC were markedly reduced after treatment with pargyline (75 mg/kg, i.p., 17 hr) and pargyline plus reserpine (75 mg/kg, i.p., 17 hr plus 5 mg/kg, i.p., 18 hr) compared to controls. However, the depletion of 5-S-cysteinyl adduct was less severe than that of DOPAC, suggesting a slower turnover of the adduct. Dopamine and 5-S-cysteinyl-DA increased significantly and to the same extent in the striatum, after pargyline alone. In the limbic system DA was significantly increased, whereas no change was found for levels of 5-S-cysteinyl-DA. 5-S-Cysteinyl-DOPA decreased significantly in the striatum after treatment with pargyline plus reserpine and non-significantly after pargyline alone. The data are compatible with a slight inhibitory effect of MAO inhibition on catechol autoxidation. This effect was, however, overridden by the increased level of DA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Hypothalamic monoamines and neuropeptides in dementia.

The concentrations of monoamines and various neuropeptides were determined in the hypothalamus of brains from patients with Alzheimer's disease and vascular dementia (n = 26) and compared with control values (n = 21). Decreased concentrations of 5-hydroxyindoleacetic acid (P less than 0.05) and homovanillic acid (P less than 0.01) were found, and increased arginine vasopressin- (P less than 0.01), galanin- (P less than 0.05) and somatostatin- (P less than 0.01) like immunoreactivity. It is proposed that this disequilibrium may be important for certain circadian symptoms, e.g. the changes in sleep/wake rhythms that are rather often observed in dementia.

Aged↗
PubMed1991

Digital amputation, replantation, and cold intolerance.

In a controlled, retrospective, clinical study, the relationships between traumatic digital amputation, digital replantation, and cold intolerance were investigated. The results of the investigation indicate that cold intolerance is a major reason for disability after digital amputation. They also indicate that the cold intolerance experienced after digital replantation is due to the original injury, and that it is not aggravated by the reconstructive surgery. Cold intolerance, in and of itself, is not a contraindication to digital replantation, regardless of whether the patient lives or works in high- or low-temperature environments.

Adolescent↗