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Biomedical subjects

P Lindberg

Publications and source records attributed to P Lindberg.

At least 73 records · Page 4Linked to original sources
PubMed1984

8-Hydroxy-2-(alkylamino)tetralins and related compounds as central 5-hydroxytryptamine receptor agonists.

A series of 2-(alkylamino)tetralins related to 8-hydroxy-2-(di-n-propylamino)tetralin (21) were prepared and tested as dopamine (DA) and 5-hydroxytryptamine (5-HT) receptor agonists. Several of the compounds were potent 5-HT agonists devoid of DA-mimetic effects. N-Ethyl or N-propyl substitution of 8-hydroxy-2-aminotetralin gave the most potent agonists. It was shown that the most potent compound, (+)-21, has the 2R configuration. 5,8-Di-methoxy-2-(di-n-propylamino)tetralin (31) was found to be a weak DA agonist devoid of 5-HT activity. The corresponding indan derivative, 4,7-dimethoxy-2-(di-n-propylamino)indan (39), has been reported to be active on both DA and 5-HT receptors. The 5-HT-stimulating properties of compounds 21 and 39 as compared to the incapability of compound 31 to activate the 5-HT receptor is tentatively explained by the assumed mode of binding of the compounds to the 5-HT receptor.

Animals↗
PubMed1984

C1-Methylated 5-hydroxy-2-(dipropylamino)tetralins: central dopamine-receptor stimulating activity.

C1-Methylated derivatives of the potent dopaminergic agonist 5-hydroxy-2-(di-n-propylamino)tetralin (6) have been synthesized and tested for central dopamine (DA) receptor stimulating activity, by using biochemical and behavioral tests in rats. Both cis- and trans-5-hydroxy-1-methyl-2-(di-n-propylamino) tetralin (4 and 3) may be classified as central DA-receptor agonists, albeit of lower potency than 6. The results obtained indicate that both 4 and 3 display DA-autoreceptor stimulation capacity. However, only one of the isomers, trans-3, is able to elicit clear-cut postsynaptic DA receptor agonist actions at larger doses. 5-Hydroxy-1,1-dimethyl-2-(n-propylamino) tetralin (5) was found to be inactive.

Animals↗
PubMed1984

Resolved 3-(3-hydroxyphenyl)-N-n-propylpiperidine and its analogues: central dopamine receptor activity.

Seven enantiomeric pairs of N-alkyl analogues of 3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP, 12) have been synthesized and evaluated pharmacologically (biochemistry and behavior) in order to examine their ability to interact with central dopamine (DA) receptors, particularly DA autoreceptors. In the R series it seems as if all compounds behave as classical DA receptor agonists with affinity and intrinsic activity for both pre- and postsynaptic receptors. The same bifunctional profile seems to be valid for the S enantiomers with N-substituents larger or bulkier than n-propyl. Likewise, the S enantiomers with ethyl or n-propyl N-substituents seem to have affinity for both pre- and postsynaptic receptors. In the total series, (S)-(-)-3-PPP [(S)-12] seems to be the most interesting compound both from the theoretical and the therapeutical point of view, possibly attenuating DA function in two different ways by stimulating the presynaptic receptors and blocking the postsynaptic receptors. This compound has been selected for extended pharmacological studies as a potential antipsychotic drug.

Animals↗
PubMed1984

Tinnitus--incidence and handicap.

A questionnaire investigation, comprising 1091 patients, was conducted at a hearing centre. A majority of patients, 59%, claimed that they were troubled by tinnitus. A strong correlation was found between the laterality of tinnitus and that of subjective hearing loss. Neither a greater degree of hearing loss nor a longer duration of tinnitus was shown to be associated with more severe tinnitus. Among patients with both subjective hearing loss and tinnitus, 23% stated that tinnitus was the greater problem and 38% that their tinnitus and hearing loss were equally troublesome. The corresponding figures for patients with hearing impairment of such a degree that a hearing aid had been fitted were 9% and 41% respectively. Stress symptoms such as headache, tension of facial muscles and sleep disturbances were correlated to tinnitus. Psychosomatic complaints should therefore be taken into account in the treatment of tinnitus. Of patients with tinnitus, 83% were interested in obtaining treatment for their tinnitus. It is postulated that the previously reported predominance of left-sided tinnitus is due to a higher frequency of left-sided hearing impairment. A majority of patients with tinnitus and hearing impairment regarded their tinnitus as the major problem. Efforts towards investigation and treatment of tinnitus might therefore considerably improve the prospects for hearing rehabilitation.

Hearing Aids↗
PubMed1984

Vitamin E requirement of mink with special reference to tocopherol composition in plasma, liver, and adipose tissue.

Tissue responses of 4 different tocopherols found in a basal diet (BD) and the effect of 2 physiologic levels of dl-alpha-tocopheryl acetate (25 and 150 mg/kg) on tissue tocopherol content were studied in the mink. The BD contained a total of 7.1 mg vitamin E/kg, with alpha-, beta-, gamma-, and delta-tocopherol in a ratio of 1:0.07:0.55:0.10, respectively. The corresponding ratios in the tissues were: liver, 1:0.04:0.12:0; plasma, 1:0:0.13:0; and adipose tissue, 1:0:0.19:0. After mink were fed diets containing vitamin E, alpha- and gamma-tocopherol were distributed in similar proportions in plasma and liver, but gamma-tocopherol was in a slightly higher proportion in adipose tissue. Addition of 25 or 150 mg/kg of alpha-tocopheryl acetate to the BD decreased the gamma-tocopherol levels in all 3 tissues; this was considered to be a dilution effect of other tocopherols in BD with added alpha-tocopheryl acetate. The beta-tocopherol content in the liver remained unchanged, irrespective of the dietary amount of alpha-tocopheryl acetate. Plasma alpha-tocopherol had a linear relationship to log dietary dose, with an apparent half-saturation of the vitamin E binding capacity at 13 mg vitamin E/kg diet. At the given dietary levels, liver and adipose continued to accumulate alpha-tocopherol. The correlation between total plasma lipids and plasma alpha-tocopherol was significant (P less than 0.001) only in the group fed the BD. Vitamin E analysis of plasma could be used as a routine method for controlling the vitamin E status of mink.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1983

Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP.

The two enantiomers of the putative centrally acting dopamine (DA) autoreceptor agonist 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP (Hjorth et al. 1981), were pharmacologically evaluated. An extensive series of biochemical and behavioural experiments unexpectedly revealed that both (+)- and (-)-3-PPP showed clear, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA agonist with autoreceptor as well as postsynaptic receptor stimulatory properties. In contrast, although (-)-3-PPP similarly activates DA autoreceptors it acts concomitantly as an antagonist at postsynaptic DA receptors. Moreover, both behavioural and biochemical data on motor activity and DA synthesis and turnover suggest a preferential limbic action for the (-)-enantiomer. These results are discussed in terms of the dual antidopaminergic action of (-)-3-PPP coupled with anatomical differences in the feedback organisation in central (viz, limbic vs striatal) DA systems. It is suggested that compounds like (-)-3-PPP may be of potential clinical utility in the treatment of psychotic disorders, whilst lacking the seriously incapacitating motor dysfunctions produced by current neuroleptic therapy.

Animals↗
PubMed1983

The effect of the enantiomers of 3-PPP on conditioned avoidance responding in the rat.

The effects of the enantiomers of 3-PPP on the maintenance of conditioned avoidance responding (CAR) were studied. The weak classical dopamine (DA) agonist (+)-3-PPP failed to interfere with CAR at any dose tested (0.8-13.6 mg/kg). Low doses of the drug produced sedation, while high doses produced behavioural stimulation. (-)-3-PPP, which acts as an antagonist on postsynaptic and as an agonist on autoreceptor DA sites, reduced avoidance with no effect on escape behaviour (6.8-13.6 mg/kg). However, this reduction of CAR occurred at doses much higher than those previously demonstrated to inhibit locomotor activity. This profile is discussed in relation to the behavioural effects of classical postsynaptic DA receptor antagonists.

Animals↗
PubMed1983

The effect of pretreatment with vitamin E on the effects of endotoxin in rat.

Twenty male rats weighing about 100g were treated subcutaneously with 25 mg alpha-tocopherol acetate. The rats were given 0.4 mg/100 g endotoxin intraperitoneally 24 hrs after the pretreatment, and were sacrificed 18 hrs after the endotoxin injection. The lipid peroxide level as evaluated by the TBA-value remained at the no-treatment level. In a similar group of rats not pretreated but given the same dose of endotoxin intraperitoneally, the TBA-value rose significantly. There were no statistically significant differences in the mean plasma ALAT and OCT activities or in the mean liver or plasma Zn concentrations between the endotoxin treated groups. The plasma OCT and ALAT activities were significantly correlated with the liver TBA-values in both endotoxin-treated groups but the plasma Zn and OCT, or plasma Zn and ALAT were significantly correlated only in the group pretreated with vitamin E. In a control group of 20 animals not treated with either endotoxin or vitamin E the plasma Zn and vitamin E concentrations were statistically significantly (P less than 0.05) correlated. It is suggested that the endotoxin effect on the liver is probably mediated by prostaglandin-like substances.

Alanine Transaminase↗
PubMed1983

The search for selective dopaminergic autoreceptor agonists.

In the course of a search for new selective dopamine (DA) autoreceptor agonists the DA analogue 3-(3-hydroxyphenyl)-N-n-propylpiperidine, 3-PPP, was resolved into its dextro-(+) and levo-(-) rotatory enantiomers. The compounds were pharmacologically evaluated by means of behavioural and biochemical methods. Surprisingly, both (+)-and (-)-3-PPP show clearcut, but differential, effects on the DA receptors. Thus, (+)-3-PPP is a DA receptor agonist with activity on autoreceptors as well as postsynaptic receptors, whereas (-)-3-PPP similarly activates DA autoreceptors but, in contrast, concomitantly acts as an antagonist on postsynaptic DA receptors. Moreover, the behavioural/biochemical profile seems to indicate a preferential limbic action for the (-)-enantiomer. Such an action could be explained on the basis of different feedback arrangements in the nigrostriatal and mesolimbic DA systems and it is suggested that compounds such as (-)-3-PPP may find future clinical application as "second-generation" antipsychotic agents, lacking in the debilitating motor side effects produced by drugs in current therapeutic use.

Animals↗
PubMed1983

The effect of colistin feeding during the mating, gestation and lactation periods on whelping result in mink.

Colistin (100000 IU/kg) was given in the feed during the mating, gestation and lactation periods to 49 female standard minks. 99 similar animals served as control without the antibiotic. The whelping result, expressed as the number of puppies living three weeks post partum per mated female, was 3.22 in the experimental group and 2.67 in the control group. The difference in the whelping result between the groups was mainly due to the significantly greater number of empty females in the control group compared to the experimental group.

Animal Feed↗
PubMed1982

A behavioural study of the changes in the central nervous system of mice after subchronic treatment with the selective dopamine autoreceptor agonist 3-PPP (dl-3-[3-hydroxyphenyl]-N-n-propylpiperidine).

In naive mice the selective dopamine (DA) autoreceptor agonist 3-PPP (dl-3-[3-hydroxyphenyl]-N-n-propylpiperidine) produced a dose-dependent depression of locomotor activity. The duration of action of the depression was short, with no significant depression being noted one or more hours after a dose of 23.47 mg/kg (expressed as the base). Mice, administered the drug twice daily (23.47 mg/kg, in the morning and the evening, i.p.) for 5 days, were, 15 to 25 hours after the last dose, marginally less sensitive to the locomotor depressant effects of a challenge with the same drug. There was no change in the sensitivity of postsynaptic DA and alpha-adrenergic receptors, as assessed by the locomotor stimulant effects of apomorphine and apomorphine plus clonidine, respectively, in reserpine and alpha-methyltyrosine pretreated animals. However, 3-PPP-pretreated mice were most sensitive to the activating effects of d-amphetamine, and this increased sensitivity was blocked by pretreatment with reserpine. In naive mice, a low, DA autoreceptor selective dose of haloperidol (25 micrograms/kg) potentiated the locomotor stimulant effects of d-amphetamine. One explanation for the data obtained is that subchronic pretreatment with 3-PPP produced DA autoreceptor subsensitivity with no concomitant change in postsynaptic DA or alpha-adrenergic receptor sensitivity. The increased sensitivity to d-amphetamine in the 3-PPP pretreated mice may be due to a reduction in the feedback control exerted by the DA released by the d-amphetamine due to the DA autoreceptors having become subsensitive.

Animals↗
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

Activities of some enzymes in the tissues of the blue fox (Alopex lagopus).

The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ornithine carbamoyltransferase (OCT), sorbitol dehydrogenase (SDH), gamma-glutamyl transferase (GGT), alkaline phosphatase (AP), lactate dehydrogenase (LDH) and creatine kinase (CK), were determined in eight organs of 10 healthy male blue foxes. OCT was absolutely liver specific and ALT was also found to be liver specific. SDH was also found primarily in the liver but its activity was relatively low. GGT was found almost exclusively in the kidneys. The highest levels of AP were observed in the kidneys and in the intestines. LDH together with AST was present in high activities in all the tissues tested. CK activity was highest in skeletal and cardiac muscles.

Alanine Transaminase↗