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Biomedical subjects

S B Ross

Publications and source records attributed to S B Ross.

At least 163 records · Page 9Linked to original sources
PubMed1978

Selective monoamine oxidase inhibitors. 1. Compounds related to 4-aminophenethylamine.

A series of derivatives of 4-aminophenethylamine was synthesized and their effect on monoamine oxidase (MAO) activity in the brain was evaluated. Several of the new compounds were potent and selective inhibitors of the A form of MAO but were poor inhibitors of the B form. The most active compounds were the 2,6-dichloro-(9) and the 2-halogeno-4-dimethylaminophenethylamines (5, 6, and 8). Some of the compounds also strongly antagonized aggressive behavior in isolated male mice. This effect was correlated to the MAO inhibition when tyramine was used as substrate. Significant correlations between MAO inhibition in vivo and potentiation of the syndromes produced by 5-hydroxytryptophan and tryptamine and antagonism of reserpine sedation were obtained.

5-Hydroxytryptophan↗
PubMed1978

Antidepressant agents. 9. 3,3-Diphenylcyclobutylamines, a new class of central stimulants.

3,3-Diphenylcyclobutylamine (4), N-methyl-3,3-diphenylcyclobutylamine (6), and N,N-dimethyl-3,3-diphenyl-cyclobutylamine (7) have been prepared and tested as potential antidepressant agents. The secondary (6) and tertiary (7) amines strongly decrease the accumulation of NA and 5-HT in brain slices in vitro and in vivo. The cyclobutylamines also cause motor stimulation. The most potent compound in this respect is the tertiary amine 7. The increase in locomotion is not blocked by pretreatment with phenoxybenzamine, methergoline, or alpha-methyltyrosine. Pretreatment with pimozide or reserpine reduces the hyperactivity induced by 7. This hyperstimulation seems to be caused by a mechanism of action which differs from that of amphetamine. 7 may cause increase in locomotion by release of dopamine from granular stores.

5-Hydroxytryptophan↗
PubMed1978

Inhibitors of neuronal monoamine uptake. 2. Selective inhibition of 5-hydroxytryptamine uptake by alpha-amino acid esters of phenethyl alcohols.

A series of alpha-amino acid esters of substituted phenethyl alcohols was prepared and tested as inhibitors of the neuronal reuptake of noradrenaline and 5-hydroxytryptamine. Some of the compounds are potent and very selective in blocking the 5-hydroxytryptamine uptake, as evidenced by biochemical data and behavioral tests. The most promising agent, alaproclate [2-(4-chlorophenyl)-1,1-dimethylethyl 2-aminopropanoate hydrochloride (I, IV)], was selected for further studies as a potential antidepressant agent. A discussion on structure--activity relationships (SAR) is given. In an attempt to explain the selective action on the mechanism of 5-hydroxytryptamine uptake by the new inhibitors, their structures are compared with those of the two neurotransmitters. From the tentative pharmacophore and conformations of transmitter (5-HT) and inhibitor (alaproclate) derived from SAR, a hypothetic carrier site for 5-HT uptake is deduced in terms of geometry and electronic properties.

Animals↗
PubMed1978

Effect of (+)-amphetamine on the retention of 3H-catecholamines in slices of normal and reserpinized rat brain and heart.

The effect of reserpine on the inhibition by (+)-amphetamine and cocaine of the accumulation of 3H-dopamine (DA) in striatal slices and 3H-noradrenaline (NA) in slices of cerebral occipital cortex and heart atrium of rats and the release of 3H-amines from these tissues were examined. Reserpine (5 mg/kg intraperitoneally) was injected 18 hours before the experiments. It was found that reserpine markedly enhanced the in vitro potency of amphetamine in the striatum and heart but only slightly in the cortex. After administration in vivo (+)-amphetamine was about 10 time more potent in reducing the amine accumulation in the cortex as in the striatum. Reserpine enhanced the effect in both regions. The inhibitory potency of cocaine in vitro was unchanged by reserpine in the striatum but was reduced in the cortex and heart. Reserpine did not change the inhibitory potency of desipramine in the cortex and heart. The release of the 3H-amines by (+)-amphetamine was enhanced by reserpine in the striatum and heart but the small release produced in the cortex was not increased. The release produced by cocaine was similarly enhanced by reserpine but cocaine was much less active than (+)-amphetamine. The results indicate that (+)-amphetamine and cocaine inhibit the amine accumulation by different mechanisms.

Animals↗
PubMed1978

Serum dopamine-beta-hydroxylase in affective disorders.

Serum dopamine-beta-hydroxylase (DBH) activity was tested in 160 psychiatric patients suffering from affective disorders. The patients were divided into subgroups according to strict diagnostic criteria and clinical state at the time of the examination. Since no relationship was found between DBH activity and age or sex, these variables have been discarded from further analyses. Bipolar (manic-depressive) patients had lower (p less than 0.05) BDH mean values than patients suffering from unipolar, recurrent depressive psychoses. No other differences were found either among group or in relation to the clinical state. As such a wide range of DBH values was recorded in all the groups examined, measurements of DBH activity do not seem to be useful as a diagnostic acid, or as an indicator of the clinical state of patients suffering from affective disorders.

Adult↗
PubMed1977

Evoked efflux of 3H-bretylium by sympathomimetic amines from the rat vas deferens in vitro.

The efflux of 3H-bretylium in rat vas deferens in vitro evoked by a number of sympathomimetic amines was examined. The tissue was preloaded with 3H-bretylium (2 x 10(-7) M) and the efflux of bretylium to the incubation medium in the presence of the amines during 20 min, was determined. The efflux evoked by (+)-amphetamine was almost abolished at 0 degrees and by desipramine. The dose response curves showed that some of the amines at high concentrations markedly antagonized their own effect. It could be demonstrated that (+)-amphetamine and N-methylamphetamine at a high concentration also antagonized the efflux evoked by low external Na+ concentrations and it is suggested that this effect is produced by inhibition of the outward transport of bretylium through the neurone membrane. The structure activity relationship obtained shows that the non-hydroxylated amines are most potent in evoking bretylium efflux and that the potency diminished with the number of hydroxyl groups. The tertiary amine analogue of amphetamine is less active and the quaternary derivative much less active than amphetamine and N-methylamphetamine. A hydroxyl group at 3-position gives a somewhat higher potency than that at 4-position. This structure activity relationship is similar to that previously reported for the sympathomimetic amines in reversing the adrenergic neurone blockade for bretylium and it is proposed that this reversal is induced by the reduction of the intraneuronal concentration of bretylium as a result of the evoked efflux.

Amphetamine↗
PubMed1977

Substituted amphetamine derivatives. II. Behavioural effects in mice related to monoaminergic neurones.

The effects of the amphetamine derivatives (+/-)-amphetamine (A), 2-, 3- and 4-chloroamphetamine (CA), 4-methylamphetamine (MA) and chlorphentermine (CP) in producing central stimulation (increase in motor activity), antagonism of the reserpine syndrome, potentiation of 1-dopa and 5-hydroxytryptophan (5HTP) responses in mice were investigated. The inhibitors of the membrane amine uptake despramine (DMI) and chlorimipramine (CI) were also included in the study. It was found that the order in central stimulating potency was A greater than 3-CA = 4-CA greater than MA greater than CP. 2-CA, DMI and CI decreased the motor activity. All the compounds potentiated the 1-dopa response with the order of activity: 4-MA greater than A greater than 2-CA = 3-CA = 4-CA = CI greater than or equal to DMI greater than CP. The decrease in motor activity (sedation) produced by reserpine was only reversed by A greater than or equal to 3-CA greater than 2-CA. alpha-Methyltyrosine but not parachlorophenylalanine, antagonized the reversal effect. Three of the compounds (3-CA, 4-CA and MA) produced head-twitches in the reserpinized mice. The 5-HTP syndrome was potentiated in order of potency by MA = 4-CA greater than CI greater than CP greater than 3-CA whereas A, 2-CA and DMI had no effect.

5-Hydroxytryptophan↗
PubMed1977

Efflux of 5-hydroxytryptamine from synaptosomes of rat cerebral cortex.

The efflux of 3H-5-HT from a crude synaptosome preparation of the cerebral cortex of reserpinized rats was examined. The synaptosomes were loaded with 3H-5-HT by pre-incubation of the homogenate in presence of pargyline and desipramine in order to inhibit deamination of 5-HT and uptake into noradrenergic neurons. The synaptosomes were collected by centrifugation, washed and resuspended in 0.25 M sucrose. No spontaneous efflux of 5-HT was detectable at 0 degrees C but marked efflux was observed at 27 degrees C and 37 degrees C. 4-Chloroamphetamine, low external Na+ concentration, ouabain and the depolarizing agent veratridine markedly accelerated the initial (5 min) efflux. Inhibitors of the neuronal 5-HT uptake, e.g. chlorimipramine, H 102/09 and A 23189, antagonized the 5-HT efflux evoked by these means, whereas desipramine, which is a poor inhibitor of the 5-HT uptake, had only slight effect on the 5-HT efflux. It is suggested that 5-HT can be actively transported out from the synaptosomes by the reversed 5-HT uptake mechanism.

Alanine↗