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Biomedical subjects

T Lewander

Publications and source records attributed to T Lewander.

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

Dopamine metabolism in red blood cells in schizophrenia.

A method was developed for the separation by thin-layer chromatography of 14C-labelled 3-methoxy, 4-hydroxyphenethylamine, 3-hydroxy, 4-methoxyphenethylamine and 3,4-dimethoxyphenethylamine (DMPEA) after incubation of dopamine with catechol-O-methyltransferase (COMT) in lysates of human red blood cells (RBC). 14 C-methyl-S-adenosyl-menthionine was used as the methyl donor. Total COMT activity with noradrenaline or dopamine as substrates, respectively, and the pattern of 14C-methylated metabolites of dopamine were measured in RBC of 47 schizophrenic patients and in 34 control subjects. There were no differences between patients and controls. DMPEA was not formed by RBC in schizophrenic patients (or in controls), a finding which argues against the "pnk spot"/DMPEA hypothesis of schizophrenia. The methods used seem suitable for studies of other human disorders where COMT might be involved.

5-Methoxytryptamine↗
PubMed1978

Tolerance to alpha-methyl-p-tyrosine in rats: studies on the antagonism of amphetamine-induced motor activity and excitatory behaviour.

Rats were treated chronically with alpha-methyl-p-tyrosine methyl-ester HCl (alpha-MT) twice daily for 0--14 days. At 1 h after the (last) alpha-MT injection, d-amphetamine sulphate was given and motor activity was measured in an ANIMEX activity meter for 4 h. Amphetamine-induced excitatory and stereotyped behaviour was scored according to a rating scale in a separate experiment. A single dose of alpha-MT markedly reduced the activity response after amphetamine. After 1--3 days of alpha-MT treatment, tolerance to its amphetamine-antagonistic affect started to develop, reaching a maximal degree after 7--14 days. The pattern of the amphetamine response, monophasic in control rats, became biphasic in the alpha-MT tolerant rats with an early (at 0--1 h) and a late (2--4 h) peak of motor activity. The late peak appeared within 3 days, while the early peak appeared after 7 days of alpha-MT treatment. The results on amphetamine-induced excitatory and stereotyped behaviour in essence agreed with the motor-activity data. It is concluded that tolerance to the amphetamine-antagonistic action of alpha-MT is not complete. Its rate of development varies in a complex pattern, indicating the presence of more than one mechanism of tolerance.

Animals↗
PubMed1978

Inhibition of the in vivo biosynthesis and changes of catecholamine levels in rat brain after alpha-methyl-p-tyrosine; time- and dose-response relationships.

Male Sprague-Dawley rats were given 0.407 mmoles/kg of D,L-alpha-methyl-p-tyrosine methylester HCl (H44/68; alpha-MT) at eleven time-points between 0--24 h, or 8 doses between 0.013--1.628 mmoles/kg of the drug at 1 h before i.v. injection of 160 micronCi tyrosine-2,6-3H. The rats were killed 15 min after tyrosine-3H and brain alpha-MT, tyrosine and catecholamines (endogenous and labelled), and plasma alpha-MT and tyrosine (--3H) were chromatographically isolated before being assayed spectrophotofluorimetrically (endogenous) or by liquid scintillation methods (labelled compounds). A delayed penetration of alpha-MT from plasma into brain, different elimination rates of alpha-MT in plasma and brain, and decreasing brain/plasma drug concentration on increasing alpha-MT dosages, indicated, that alpha-MT in brain and plasma belong to different pharmacokinetic compartments. The endogenous levels of catecholamines in the time-response experiments, declined to a minimum 4 h after alpha-MT administration, where the dopamine level was 38% and the noradrenaline level 51% of the saline controls. Kinetic data of the catecholamine elimination is given. In the dose-response experiment the decrease in the endogenous catecholamine levels was dose-related up to 0.407 mmoles/kg of alpha-MT, with no further decline on higher doses. The maximal inhibition of brain catecholamine synthesis occurred within 30 min after alpha-MT administration and the inhibition correlated better with the brain than with plasma alpha-MT content. The inhibition was dose-related with a maximal synthesis inhibition of 95% for dopamine and 80% for noradrenaline at the highest dose of alpha-MT. The duration of synthesis inhibition and storage depletion were shorter for noradrenaline (12 h) than for dopamine (16 h). Further, the ED50 for synthesis inhibition of dopamine (0.057 mmoles/kg) was half of the ED50 for synthesis inhibition of noradrenaline (0.117 mmoles/kg). This might suggest different sensitivities towards alpha-MT or different availabilities of alpha-MT in the two neuron populations. At the three highest doses of alpha-MT there were signs of interference with the uptake process for tyrosine from plasma into the brain. This was indicated by increased plasma levels and decreased brain levels of tyrosine (--3H).

Animals↗
PubMed1978

The relationship between amphetamine antagonism and depletion of brain catecholamines by alpha-methyl-p-tyrosine in rats.

The time-course and the dose-response relationship for the antagonistic effect of alpha-methyl-p-tyrosine methyl ester HCl H 44/68 (alpha-MT) on d-amphetamine (10.6 mumoles/kg) induced increase in motor activity was studied. The effect of amphetamine was gradually reduced from 30--60 min to a minimum at 1--4 h after the administration of 0.407 mmoles/kg of alpha-MT. From (4--) 8 h the amphetamine response started to reappear and the original response was restored completely at 16 h after alpha-MT. The dose-response curve showed, that between 0.051--0.41 mmoles/kg of alpha-MT, given 1 h before amphetamine, there was a gradual reduction of the amphetamine response; doses above 0.41 mmoles/kg did not cause any further effect. The antiamphetamine action of alpha-MT was compared with its time- and dose-dependent effects of inhibition of synthesis and reduction of stores of brain catecholamines. It was found, that the antiamphetamine action was more closely correlated with the reduction of the levels of brain dopamine, than with the brain noradrenaline levels. Further, the inhibition of catecholamine synthesis per se did not appear to be a sufficient condition for alpha-MT induced antagonism of amphetamine. These findings support the view that amphetamine is dependent on a substantial portion of the brain pool of dopamine and possibly noradrenaline rather than on very small, newly synthesized pools of these neurotransmitters.

Animals↗
PubMed1977

Tyrosine hydroxylase: delayed activation in central noradrenergic neurons and induction in adrenal medulla elicited by stimulation of central cholinergic receptors.

The centrally active muscarinic agonist, oxotremorine, elicited an up to 2-fold dose-dependent (0.25-1.5 mg/kg) increase in the activity of tyrosine hydroxylase (TH) in the rat nucleus locus coeruleus (LC) and adrenal medulla. The response occurred in LC after 24 to 48 hours and in adrenal medulla by 4 to 8 hours, peaked in LC at 72 hours and adrenal medulla at 16 to 24 hours and persisted up to 2 weeks in both tissues. In brain the effect appeared confined to cell bodies of noradrenergic neurons. The activity of dopamine beta-hydroxylase increased in adrenal medulla (40%) but not in brain. Immunotitration with anti-TH serum demonstrated that the increase of TH activity in LC is due to increased catalytic activity (activation), whereas in adrenal medulla it is due to a transynaptically mediated accumulation of enzyme protein (induction). Physostigmine (1.0 mg/kg), pilocarpine (25-50 mg/kg) and nicotine (10 mg/kg) increased TH activity in LC and adrenal. We conclude that stimulation of central cholinergic receptors of the muscarinic type results in a delayed and protracted activaiton of TH but not of dopamine beta-hydroxylase in cell bodies of central noradrenergic neurons, and reflexly, to transynaptic induction of TH and dopamine beta-hydroxylase in the adrenal medulla.

Adrenal Medulla↗
PubMed1975

The duration of tolerance to the anorexigenic effect of amphetamine in rats.

Rats were given dl-amphetamine 16 mg/kg twice daily for 15 days. Complete tolerance to the anorexigenic effect of amphetamine developed from day 7--11. A single injection of 16 mg/kg amphetamine was given to the amphetamine pretreated rats and to saline pretreated controls at different time-points after withdrawal, and their food intakes were compared. Signs of tolerance were present in 16 but not 20 days after withdrawal.

Amphetamine↗