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[Prolonged administration of antidepressants induces changes in the pulsed release but not in the reverse uptake of biogenic amines].

The experiments on rats have shown that antidepressant concentrations that cause 50% inhibition of 14C-NA and 3H-HT uptake by brain slices remain unchanged following prolonged administration of antidepressants (imipramine, pirazidole, harmane and its derivatives--C-153, C-307, C-394, C-395), as compared to the control. Electrical stimulation of brain slices upon long-term treatment of rats with antidepressants and preincubation with 14C-NA and 3H-HT enhanced presynaptic release of radioactive mark at concentrations of antidepressants (EC2) 3-14 times lower than those in the control animals. Long-term antidepressant administration reduces the inhibitory influence of clonidine and HT on presynaptic release of 14C-NA and 3H-HT by brain slices. It is suggested that long-term administration of antidepressants decreases the sensitivity of terminal axons of NA- and HT-ergic neurons to autoinhibitory effect of neurotransmitter release.

Animals↗

[Changes in the activity of cortical neurons after administration of biogenic amines].

Effects of different neurotransmitters on activity of cortical neurons were studied in immobilized rabbits. The final effect of serotonin and noradrenaline, in contrast to acetylcholine and GABA, depended on initial functional level of the neurons. Various types of cortical neurons responses to the same monoaminergic stimuli are described. The comparative analysis of the data obtained suggests participation of serotonin and noradrenaline in neurochemical organization of positive and negative reinforcement, resp.

Acetylcholine↗

Relationships between drug-induced changes in tetrahydrobiopterin and biogenic amine concentrations in rat brain.

In vitro studies of rat brain tyrosine hydroxylase and tryptophan hydroxylase activities have demonstrated nonlinearities in both time course and substrate velocity curves that were sensitive to small changes in tetrahydrobiopterin (BH4) concentrations when studied within a range speculated to approximate the in vivo condition. High-performance liquid chromatographic determinations of rat striatal BH4 levels reported here are consistent with such a nonlinear relationship of BH4 and brain monoamine synthesis under four in vivo conditions: 1-day s.c. amphetamine infusion, L-tryptophan loads, i.v.t. administration of corticotropin releasing factor and the diurnal rhythms of the dopaminergic nigrostriatal and serotonergic raphe hippocampal systems. Only the results of continuous 10-day amphetamine infusion were consistent with a simple stoichiometric relationship between the (postulated) rate limiting concentrations of BH4 and regional levels of brain monoamines. Although some of the statistically significant changes in regional brain BH4 levels are small, previous reports of the failure of biopterin to change in response to more than 30 other central nervous system drugs, including such stimulants as methylphenidate and cocaine, makes them noteworthy.

Animals↗

[Organ distribution of ruthenocenyl biogenic amine derivatives--radiodiagnostic agents for the adrenals and ovaries?].

The organ distribution of 103Ru labelled ruthenocenyl derivatives of tyramine, histamine, benzylamine, phenylethylamine and homoveratrylamine were measured in rats. The derivatives of tyramine, histamine and benzylamine showed a high affinity for the adrenal and ovar. Adrenal/muscle ratios up to 2000:1 were gained but only if the dose was administered i.v. and was below 0.1 mumol/kg. The ruthenocenyl derivatives of tyramine labelled with 103Ru in the ruthenocene moiety or with 14C in the tyramine moiety showed a parallel distribution pattern but completely different from the distribution of 103RuCl3. This indicates that the tyramine derivatives are not destroyed in the body yielding Ru-ions. The advantages of the ruthenocenyl derivatives in comparison with the known amphetamine derivatives labelled with radioactive iodine are discussed.

Adrenal Glands↗

[Defect in deamination of biogenic amines in spontaneous hypertension].

Activity of monoamine oxidases (MAO) of the types A and B (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) has been studied in mitochondrial fractions from brain, heart, liver and kidney of 24-week-old rats of the normotonic strain Wistar Kyoto (WKY) and spontaneously hypertonic rats (SHR). As compared with the WKY rats, in the SHR strain the activity of MAO-A in heart mitochondria was increased 1.5-1.7-fold; in liver mitochondria the activities of both MAO-A and -B were increased 2.6-2.7-fold. In brain mitochondria there was noted only slight tendency towards an increase in MAO-A (substrate: 5-hydroxytryptamine) and MAO-B (substrate: 2-phenylethylamine) activities in the SHR strain as compared with the normotonic animals of the same age. However, in experiments with tyramine as a substrate of MAO the enzymatic activity in SHR brain mitochondria was increased 1.5-fold (P less than 0.05) as compared with the WKY rats. In kidney mitochondria of SHR the activity of MAO (substrates: 5-hydroxytryptamine, 2-phenylethylamine, tyramine) did not exhibit any alterations as compared with the control WKY rats.

Animals↗

Effects of 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo [3,4-c]thieno[2,3-e][1,4]diazepine (Y-7131) on the metabolism of biogenic amines in brain.

A new derivative of thienodiazepine, 6-(o-chlorophenyl)-8-ethyl-1-methyl-4H-s-triazolo[3,4-c]thieno[2,3-e][1,4]diazepine (Y-7131) decreased the turnover of 5-hydroxytryptamine (5-HT) but not that of dopamine (DA) in the rat brain. The potency of Y-7131 in inhibiting the 5-HT turnover was stronger than that of diazepam. Imipramine decreased the turnover of 5-HT, whereas chlorpromazine increased the turnover of DA. Y-7131 decreased the turnover of norepinephrine (NE) in the mouse brain. With diazepam, such an action was not recognized. Imipramine did not affect the turnover of NE, whereas chlorpromazine increased it. Y-7131 inhibited the uptake of NE in the mouse brain, although it did not inhibit the uptake of 5-HT. Diazepam was devoid of such an action. Imipramine inhibited the uptake of both amines. The increase of the turnover of 5-HT, NE and DA due to foot-shock stress in the rat brain was suppressed by the administration of Y-7131. In this antagonistic effect, Y-7131 was more potent than diazepam. Neither imipramine nor chlorpromazine showed these antagonistic effects. The results obtained suggest that Y-7131 has biochemical profiles similar to diazepam but differs from it in exhibiting inhibitory effect on the NE turnover and its uptake.

Animals↗