Biomedical subjects

C Braestrup

Publications and source records attributed to C Braestrup.

99 records · Page 6Linked to original sources

PubMed1976

Regulation in the central norepinephrine neurotransmission induced in vivo by alpha adrenoceptor active drugs.

The level of the two major norepinephrine metabolites, 3-methoxy-4-hydroxyphenylglycol (MOPEG) and 3,4-dihydroxyphenylglycol (DOPEG), was estimated in the central nervous system of rats to study receptor-mediated regulation of release in vivo as reflected in biochemical changes. The norepinephrine receptor stimulating drug clonidine (0.02-0.5 mg/kg) decreased the level of endogenous total MOPEG. The accumulation of 3H-MOPEG and 3H-DOPEG was decreased by clonidine (0.5 mg/kg) regardless of whether 3H-tyrosine or 3H-dopamine was used as precursor of 3H-norepinephrine. In contrast to clonidine, the two alpha adrenoceptor blocking drugs, phenoxybenzamine (20 mg/kg) and aceperone (20 mg/kg), induced an increase in endogenous total MOPEG and also an increase in 3H-MOPEG and 3H-DOPEG regardless of the precursor used. These results indicate that clonidine decreases the release of norepinephrine in vivo and that phenoxybenzamine and aceperone increase the release of norepinephrine. Clonidine inhibited completely the effect of phenoxy benzamine or aceperone on endogenous MOPEG. On the contrary, it was not possible to block completely the effect of small doses of clonidine by pretreatment with either phenoxybenzamine, yohimbine (2 mg/kg) or a high dose of aceperone. These results indicate that clonidine may act on a different target than the alpha adrenoceptor blocking drugs. In vitro experiments with occipital cortex synaptosomes did not indicate a direct effect of clonidine on tyrosine hydroxylation in noradrenergic nerve terminals.

Animals↗

PubMed1975

The monoamine oxidase B inhibitor deprenyl potentiates phenylethylamine behaviour in rats without inhibition of catecholamine metabolite formation.

The drug l-deprenyl has been reported to have antidepressant properties, and in the present study three possible mechanisms of action were investigated in animal experiments. l-Deprenyl, which is a type B monoamine oxidase (MAO) inhibitor, was compared to clorgyline, an MAO A inhibitor with regard to its inhibitory effect on the formation of three major catecholamine metabolites, homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol (MOPEG) in the rat brain in vivo. Apart from a difference in dose levels the two drugs showed no difference in the dose--response pattern of all three metabolites. Clorgyline inhibited the formation of HVA, DOPAC and MOPEG with an ED50 of about 0.2 mg/kg s.c. and l-deprenyldopamine and noradrenaline are formed by the same type of monoamine oxidase(s), probably type A, in the rat brain in vivo. Antidepressant properties of l-deprenyl therefore seem to be independent of catecholamine deamination. l-Deprenyl but not clorgyline (2 or 8 mg/kg s.c.) potentiated the stereotyped sniffing behaviour induced by beta-phenylethylamine, a specific substrate for type B monoamine oxidase. This result is discussed in relation to a new hypothesis of phenylethylamine and dopamine involvement in depression. l-Deprenyl was 10,000 times less potent than DMI as inhibitor of noradrenaline uptake in crude synaptosomes from the occipital cortex of rat brain. Inhibition of noradrenaline uptake was therefore excluded as a possible mechanism for the antidepressant action of l-deprenyl.

Animals↗

PubMed1975

Intra- and extraneuronal formation of the two major noradrenaline metabolites in the cns of rats.

The two major noradrenaline metabolites in the rat brain, total 3-methoxy-4-hydroxyphenylglycol (MOPEG) and total 3,4-dihydroxyphenylglycol (DOPEG), were measured by a new analytical procedure after intraventricular (i.v.t.) injection of (3-H) noradrenaline or (3-H) dopamine. I.v.t. injection of (3-H) noradrenaline to rats with a 6-hydroxydopamine-induced destruction of nerve terminals in the central nervous system, resulted in an increased accumulation of 3-H-MOPEG compared to 3-H-DOPEG. On the contrary, reserpine induced a greater increase in 3-H-DOPEG than in 3-H-MOPEG accumulation when these two metabolites were formed from (3-H) noradrenaline synthesized in vivo by i.v.t. injection of (3-H) dopamine. These results indicate that the formation of DOPEG and MOPEG occur with some preference intra- and extraneuronally, respectively. The results, however, also show that these two formations sites should not be considered as specific.

Animals↗

PubMed1975

Apomorphine-induced stereotyped biting in the tortoise in relation to dopaminergic mechanisms.

A biting behavior in the Moroccan pond tortoise (Clemmys caspica leprósa) after apomorphine administration is described. The biting behavior was antagonized by the specific anti-dopaminergic drug haloperidol (10 mg/kg) and trifluperazine (15 mg/kg). The behavior was compared to similar behaviors in birds and mammals. The dopamine metabolites, homovanillic acid and 3,4-dihydroxyphenylacetic acid, were measured by a gas chromatographic method in the tortoise brain. From the effects on behavior and the changes in the level of these metabolites upon drug administration it was concluded that the dopamine system in the tortoise is qualitatively similar to that in birds and mammals but less sensitive to blockade.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1974