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Biomedical subjects

H Coper

Publications and source records attributed to H Coper.

At least 55 records · Page 3Linked to original sources
PubMed1981

Serum DBH and platelet MAO in patients with depressive disorders.

Km and V of serum dopamine-beta-hydroxylase and platelet monoamine-oxidase (MAO) were determined in the depressive and manic state as well as after recovery in patients with affective psychoses and in the depressive state of patients with neurotic depression. DBH and MAO values were measured also in age- and sex-matched controls. The Km and V values of each enzyme failed to differ between patients and healthy controls or between patients during and after an episode of illness. The ratio of V of serum DBH (tyramine as substrate) tended to be lower in patients independent of their psychopathological state than in controls. The findings fail to support the notion that characteristics of the peripheral enzymes measured provides a reliable indicator of a biological disposition to depression, but are consistent with the notion that the balance of monoamine may play a role in certain psychopathological states.

Affective Disorders, Psychotic↗
PubMed1980

Modification of different morphine actions by 6-hydroxydopamine and 6-hydroxydopamine plus desmethylimipramine.

After intracisternal 6-hydroxydopamine (6-OHDA) in mice, brain noradrenaline (NA) and dopamine (DA) are diminished, although the reduction of NA is more pronounced. Intracisternal injection of 6-OHDA in desmethylimipramine (DMI)-pretreated animals strengthens the depletion of DA while NA is partly protected. The concentration of 5-hydroxytryptamine (5-HT) is not influenced by 6-OHDA or 6-OHDA + DMI. Chronic morphine treatment to some extent enhances reduced NA and DA levels after 6-OHDA, but the decreased central catecholamine (CA) content after 6-OHDA + DMI is not raised. Morphine analgesia is highly attenuated in 6-OHDA and 6-OHDA + DMI mice. The reduction occurs in non-tolerant as well as in tolerant animals. The acute effect of morphine on body temperature is abolished with 6-OHDA, but not with 6-OHDA + DMI, whereas the interaction of central CA in morphine-induced running shows distinctly marked reduction with 6-OHDA + DMI, but not with 6-OHDA. Acute toxicity is enhanced by 6-OHDA + DMI whereas the development of tolerance against the toxicity of morphine is diminished by 6-OHDA. Lack of CA in the brain decreases sensitivity against naloxone withdrawal in acute as well as in chronic experiments.

Analgesia↗
PubMed1980

Development of dependence on levorphanol in rats by oral intake of the drug -- the influence of taste on drinking behaviour in rats physically dependent on levorphanol.

Oral administration of levorphanol solution induces physical dependence in rats within a few days, as demonstrated by abstinence symptoms such as loss of body weight, sensitivity to touch and inversion of locomotor activity after withdrawal from the drug. In order to examine whether the physically dependent rats show an active drug-seeking behaviour they were given successively free choice between sweetened levorphanol solution (LSa) and two alternative drinking liquids -- sweetened tap water (WSa) and unadulterated water (W). In the case of LSa and W the rats chose LSa, but they preferred WSa to LSa. Another group of rats made dependent on unsweetened levorphanol solution (L) had the choice between L and W. They rejected L immediately.

Animals↗
PubMed1980

The influence of p-chlorophenylalanine on different morphine effects.

p-Chlorophenylalanine (p-CPA) reduces brain 5-hydroxytryptamine (5-HT) without altering the dopamine and norepinephrine content. Morphine does not influence the 5-HT level, but partly reverses the depletion of 5-HT by p-CPA. Morphine analgesia and toxicity are not affected by p-CPA treatment. p-CPA also has no effect on acute morphine hypothermia, but after chronic treatment of 5-HT-deficient mice the dose--response curve is no longer parallel, which suggests that another mode of morphine hypothermia occurs. p-CPA diminishes morphine-induced running after acute as well as after chronic morphine administration. p-CPA treatment reduces the sensitivity to the naloxone-precipitated withdrawal reaction, but does not affect the development of physical dependence.

Analgesia↗
PubMed1980

Erythrocyte COMT-activity in patients with affective disorders.

COMT enzyme characteristics (Km, V, ratio of meta/paramethylation) were determined in the red blood cells of 20 patients with endogenous depression, in 20 healthy controls matched as to age and sex, as well as in 10 patients with mania, and 10 patients with neurotic depression. Assessment was done twice, i.e. before and after remission in patients with endogenous depression and in the manic patients. If male and female patients are considered together there was no statistical difference between the COMT characteristics of these patient groups, either before or after remission. Only the bipolar patients showed a higher COMT-activity (V) than their individually matched controls. If however, only the female patients are taken into consideration, COMT-activity of the patients with endogenous depression vs. controls is significantly increased by 60%. This difference can be demonstrated also after remission ("free interval") though statistical significance is reached only for the unipolar group. Further in vitro experiments indicate that antidepressant drugs do not possess a relevant influence on COMT-activity. Ranking the mean COMT-values leads to the following order: matched controls (< neurotic depression < unipolar depression < bipolar depression, which would be in good agreement with theoretical expectations based on the amine hypothesis of depression. Compared with normal male subjects COMT-activity of female controls is significantly lower. On the other hand, the female patients with endogenous depression show a significantly higher enzyme activity than the corresponding male patients.

Affective Symptoms↗
PubMed1980

Identification of tetrahydronorharmane (tetrahydro-beta-carboline) in human blood platelets.

The present paper shows that tetrahydronorharmane (tetrahydro-beta-carboline) exists in human platelets. The concentration of tetrahydronorharmane in platelets from 10 ml platelet rich plasma was in the range of 9.3 to 25.6 pmol (n=8). Ingestion of tryptamine hydrochloride (n=4) three times daily for three consecutive days and of 19.6 mmol D,L-tryptophan (n=7) the evening (10 p.m.) before the blood collection did not lead to an increase of tetrahydronorharmane in platelets.

Adult↗
PubMed1980

[Effectivity of drugs in the elderly with regard to their pharmacokinetics and pharmacodynamics (author's transl)].

In principle, in all periods of life drugs act with the same mechanisms. Characteristics modifications of drug effects are caused by age dependent special constellations of pathogenesis and course of the illness, as well as of the multimorbidity in relation to physiological ageing. The most important functional process of ageing is the progressively decreasing adaptability towards environmental conditions with interindividually distinct deviations. If elderly patients react quantitatively in an unexpected fashion, the reason can be a different absorption, distribution, renal or metabolic elimination of the drug. But there exists also an age dependent sensitivity towards drugs, which can be explained in a modified reaction-pattern of the receptors.

Aged↗
PubMed1979

Depression and monoamine oxidase.

1. The first part of the paper is devoted to a critical review on the possible relationships between depression and monoamine oxidase. 2. This study describes the results of an investigation of MAO-activity in depression, using new approaches and methodology. This methodology was developed because the literature data indicated that a) previous results are difficult to compare because of varying methods and diverse target populations used; b) previous methodological deficiencies do not allow to draw definite conclusions about the relationship between MAO-activity and depression. 3. The present investigation selected 35 psychiatric patients according to clearly defined diagnostic criteria (20 endogenous depressive, 10 neurotic depressive, and 5 manic patients) matched to 25 healthy control-subjects. 4. The Michaelis-constant (Km), the maximum reaction speed (Vmax), and the 50% enzyme inhibition by tranylcypromine (IC50) of platelet-MAO were determined during and after recovery from the depressive or manic episode using 3 substrates (tyramine, tryptamine, and phenylethylamine). 5. The present investigation, in contrast to conventional methodology, utilized three different substrates at different concentrations. Significant correlations were demonstrated for the Vmax-values of each of the three substrates, whereas the Km and the IC50 (tranylcypromine)-values varied for each substrate. 6. The results show that there were no differences between the characteristics of the platelet-MAO in depressive or manic patients and those of normal subjects. Furthermore, treatment with tricyclic antidepressants had no effect on MAO-activity. A previous investigation indicated that the MAO-properties in human brain tissue were similar to that in human platelets.

Adult↗
PubMed1978

Interaction between d-amphetamine and ethanol with respect to locomotion, stereotypies, ethanol sleeping time, and the kinetics of drug elimination.

The interaction between d-amphetamine and ethanol with respect to locomotor activity, stereotyped behavior, and sleeping time was investigated in rats. Ethanol 0.8 g/kg i.p. enhanced and prolonged locomotor activity produced by d-amphetamine 1 mg/kg s.c. The increased motility after 5 mg/kg d-amphetamine was not influenced by alcohol 0.8 g/kg i.p. or 3.2 g/kg orally, but slightly protracted. Stereotyped head and paw movements, as well as stereotyped licking, were distinctly strengthened and protracted by 3.2 g/kg ethanol orally. The modified d-amphetamine motility and stereotypies can be explained by alcohol-induced proloneation of the life of d-amphetomine. The effect is produced by alcohol's inhibition d-amphetamine p-hydroxylation in rat liver. After 3.2 g/kg ethanol i.p., the sleeping time of male rats amounted to 153 min. Simultaneous administration of 5 mg/kg d-amphetamine s.c. reduced the sleeping time to 84 min. This is obviously based on a central antagonism.

Animals↗
PubMed1977

Interaction between delta(9)-tetrahydrocannabinol and d-amphetamine.

d-Amphetamine increases the motor activity at a dose range of 0.5-4 mg/kg. delta(9)-Tetrahydrocannabinol (THC) diminishes this effect dose-dependently. Also, the hyperthermia caused by 5 mg/kg d-amphetamine is antagonized by THC, whereas the d-amphetamine induced stereotype movements (above 4 mg/kg) are prolonged by the cannabinoid. THC and d-amphetamine both reduce the food and water intake and the normal development body weight of rats. In combination the two substances have an additive effect. Rats treated with 5 mg/kg d-amphetamine show a significant enhancement of the dopamine (DA) concentration (26%) in the brain stem 2 h p.i. Pretreatment with 10 mg/kg THC, which also causes an increase of DA by 15%, raises the DA content by 50%. Norepinephrine (NE) in the brain stem and hypothalamus is reduced by d-amphetamine but THC has no effect on the concentration of this monoamine. After subchronical treatment with THC tolerance is demonstrable to all THC effects tested. But there is no cross tolerance between delta(9)-THC and d-amphetamine since the pharmacological as well as the biochemical effects of d-amphetamine occur despite the subchronical treatment with THC.

Animals↗
PubMed1977

The development of tolerance to morphine in the rat.

Tolerance to various effects of morphine in the rat can be quantified by means of a shift of semi-logarithmic dose-response curves. Tolerance to analgesia (hot plate, acetic acid writhing), catalepsy, and the tilted plane develops in a closely similar manner. Also, the stimulating effects of about 1 mg/kg morphine-HC1 tested in an open-field procedure are somewhat less pronounced in chronically treated rats than in naive ones. There is no correlation between tolerance development and the acute ED50 of different tests.

Animals↗
PubMed1977

Is tolerance to delta-9-THC cellular or metabolic? The subcellular distribution of delta-9-tetrahydrocannabinol and its metabolites in brains of tolerant and non-tolerant rats.

Rats were injected intraperitoneally once every 12 h with 10 mg/kg delta-9-THC and the time course of the depressant effect was determined after one and nine injections. The motor activity of naive rats was maximally depressed between 1 and 4 h and returned to control levels 8 h after treatment. After nine injections, the maximum intensity of the depressant effect was not different from that after one injection but had completely disappeared at an earlier time point (4 h p.i.) indicating the development of tolerance to the duration of effect on motor activity. The subcellular distribution studies in brains of tolerant and non-tolerant rats indicated that an accelerated shift in the concentrations of delta-9-THC and 11-OH-delta-9-THC towards highly polar metabolites in the brains, rather than an increased elimination of these cannabinoids or decreased sensitivity of the brain may be responsible for the development of tolerance to delta-9-THC.

Animals↗
PubMed1977

Formation of chlorpromazine sulphoxide and monodesmethylchlorpromazine by microsomes of small intestine.

The metabolism of chlorpromazine by microsomal preparations of the small intestine from guinea pig and rat was studied. 35S-chlorpromazine was incubated with these preparations in Krebs-Ringer bicarbonate buffer at 37 degrees C. Control values were obtained by performing the assay at 0 degrees C. The metabolites were extracted with dichloroethane and separated by TLC. In incubations with intestinal microsomes from guinea pigs chlorpromazine sulphoxide and monodesmethyl chlorpromazine were identified as main metabolites. The apparent Michaelis constant for sulphoxidation of chlorpromazine is approximately 20-30 micronM and for N-demethylation in the range of 30-100 micronM. Using microsomal preparations from rat intestine, however, noteworthy formation of chlorpromazine metabolites could not be found. This observation can be explained by the fact that the cytochrome P450 content of rat intestinal microsomes was extremely low compared with that determined in guinea pig microsomes.

Animals↗
PubMed1977

Quantitative assessment of tolerance to and dependence on morphine in mice.

1. Tolerance to morphine-induced analgesia (hot plate and acetic acid whrithing test), hypothermia and lethality can be quantified in mice by measuring the degree of parallel shifts of semilog. dose-response relationships induced by repeated opioid administration. 2. A similar procedure can be used for the quantification of naloxone-induced withdrawal as an indicator of dependence. 3. The intensity of tolerance development with respect to time of administration and dosage of morphine varies with the test procedure. It is closely parallel, however, in both analgesic tests during acquisition of tolerance. 4. Log-log-linear relationships exist between tolerance in analgesic tests and physical dependence as determined by naloxone-induced withdrawal. 5. The minimum tolerance-inducing dose of morphine in different tests could not be correlated to the ED50's in these tests. 6. Chronic opiate treatment leads to a decrease or an increase in motility response to morphine, depending on the time that has elapsed after the last morphine administration.

Analgesia↗