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H Coper

Publications and source records attributed to H Coper.

At least 19 recordsLinked to original sources
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↗
PubMed1976

The effect of chronic self-administration of d-amphetamine on food intake, locomotor activity, and C14-leucine incorporation into cerebral cortex protein.

Rats had free access to 0.02% d-amphetamine solution instead of water for 23 days. The daily amphetamine consumption was found to increase from 16 mg/kg on day 1 up to 47 mg/kg on day 23. Tolerance to the anorexic effect of the drug was apparent on day 11. The initial depression in body weight persisted throughout the experiment. The hyperactivity of rats remained at the same level despite the daily increase in amphetamine intake. The incorporation of C14-leucine into cerebral cortex proteins was initially increased and returned to control level after 2 weeks of treatment. No direct correlation between hyperactivity and brain cortex protein synthesis was observed.

Animals↗
PubMed1976

Inhibition of the reuptake of serotonin by tryptoline.

Tryptoline, a metabolite of tryptamine, competitively inhibits serotonin accumulation in nuclei-free homogenate of rat "forebrains". After intraventricular injection the drug elicits an increase of serotonin levels in the same part of the brain whereas the monoamine oxidase activity is not altered.

Animals↗
PubMed1976

Critical evaluation of measurement of platelet monoamine oxidase in man.

Some biochemical characteristics such as substrate specificity, substrate affinity and inhibitor sensitivity of monoamine oxidase of human blood platelets were investigated. Tyramine, tryptamine and beta-phenylethylamine were used as substrates. The apparent Michaelis constants, maximal velocity rates and I50 for the inhibitor tranylcypromine were determined. The data were analyzed according to Lineweaver-Burk and Dixon. The influence of amitriptyline, a prototype of tricyclic antidepressants, on the selected variables (Km, V, I50), was studied. The parameters investigated showed remarkably low interindividual differences when healthy volunteers were tested. The inhibitor activity of amitriptyline towards platelet monoamine oxidase depends on the substrate used. Amitriptyline concentrations which showed a pronounced effect on the enzyme characteristics are significantly higher than plasma levels of the drug found under therapeutic conditions.

Adult↗
PubMed1976

[Comparative pharmacological effects of dl-amphetaminil and dl-amphetamine in the rat].

The present investigation shows that amphetamine and amphetaminil produce identical pharmacological effects (increase in motility and body temperature, anorexia, stereotypic behaviour). There was neither a qualitative difference under "open field" conditions nor a difference in the capacity of modifying the reserpine induced syndrome. In isomolar doses amphetamine was somewhat more effective. Almost the same amounts of amphetamine were found in blood and brain following amphetamine or amphetaminil administration, with exception of somewhat higher peak levels after amphetamine. These results favor the hypothesis that amphetaminil effects are produced by the amphetamine molecule.

Acetonitriles↗