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Biomedical subjects

S B Ross

Publications and source records attributed to S B Ross.

At least 145 records · Page 8Linked to original sources
PubMed1981

The pharmacology of zimelidine: a 5-HT selective reuptake inhibitor.

Zimelidine (ZIM) and its main active metabolite norzimelidine (NZIM) have been shown to preferentially inhibit 5-hydroxytryptamine (5-HT) neuronal uptake both in vitro and in vivo while having much less effect on noradrenaline (NA) uptake. ZIM in vivo blocked the 5-HT uptake mechanism in the cerebral cortex, hippocampus, striatum, hypothalamus and spinal cord, thus indicating effects on both the ascending and descending 5-HT pathways. ZIM is devoid of a 5-HT releasing action, MAO-inhibitory properties and effects on dopamine (DA) uptake. ZIM failed to reduce NA turnover even in high doses, but markedly reduced 5-HT turnover in very low doses in the rat. ZIM also enhanced 5-HT mediated behaviours in mice in doses related to the inhibition of 5-HT uptake. In contrast to amitriptyline (AMI) and mianserin (MIAN), ZIM only in extremely high doses displayed a 5-HT receptor blocking action in vitro and failed to block 5-HT mediated behaviour. ZIM was practically devoid of action on histamine H1 and H2 receptors, and had also a neglible action on noradrenergic alpha 1- and alpha 2-receptors, and on beta-receptors. Unlike the tricyclic antidepressants (TAD's) ZIM had a negligible action on muscarinic receptors and failed to affect cholinergic induced activity. Long-term treatment with ZIM did not result in any attenuation of the 5-HT uptake blocking potency or the reduction of 5-HT turnover. This long-term treatment slightly reduced the number of beta-receptors in the brain. However, repeated ZIM-treatment induced a new 5-HT receptor binding site characterized by a low affinity and with a high number of binding sites and decreased the number of high affinity 5-HT receptor binding sites. Unlike the TAD's zimelidine failed to block the action of reserpine. Metabolic and behavioural interactions studies in mice showed that ZIM was devoid of any significant interactions with ethanol, barbiturates and benzodiazepines. It is concluded that ZIM markedly differs from both the TAD's and new antidepressants such as mianserin and nomifensine. ZIM seems preferentially to effect the presynaptic 5-HT reuptake mechanism while having a negligible action on noradrenergic, 5-HT, acetylcholine and histamine receptors in the brain.

Animals↗
PubMed1981

Catechol-O-methyltransferase activity in human erythrocytes: methodological aspects.

Different methodological aspects on the assay of human erythrocyte catechol-O-methyltransferase (COMT) activity were studied. No temporal variations were found either over a 24 hour period or over one month. Erythrocytes from whole blood collected with any of the anticoagulants heparin, EDTA or citrate could be used as the enzyme source provided the cells were washed in saline. The COMT activity in lysed erythrocytes was rapidly lost when the lysate was stored at +4 degrees C and -20 degrees C. Intact erythrocytes could be stored up to one week in +4 degrees C without considerable loss of activity. The COMT activity was stable for at least two years when storing the cells at -85 degrees C. Freeze-thawing and hypotonic disruption of the erythrocytes resulted in the same activity and neither freeze-thawing nor sonication altered the apparent Km for the substrate. Noradrenaline and 3,4-dihydroxybenozic acid (DBA) could both be used as substrates although DBA gave higher activity values and had a higher affinity to the enzyme. The COMT activity increased with increasing concentration of the methyl-donor S-adenosyl-1-methionine up to approximately 0.1 mM. Preincubation at 47 degrees C decreased the COMT activity whereas the apparent Km values remained unchanged. The present COMT assay was convenient and reproducible and could be used with small amounts of blood with different kinds of anticoagulants. Interactions with plasma factors were avoided by washing the erythrocytes with isotonic sodium chloride.

Anticoagulants↗
PubMed1980

Evidence for a role of the locus coeruleus noradrenaline system in learning.

The effect of the new noradrenaline (NA) neurotoxin, DSP4, on the acquisition of one-way and two-way active avoidance responses was studied in rats. This treatment caused a marked degeneration of the locus coeruleus NA system and markedly impaired both one- and two-way avoidance acquisition. Both effects were blocked by pretreatment with desipramine, a NA uptake blocking agent. The present findings support the hypothesis that the locus coeruleus NA system in its entire extent may play a role in aversive learning.

Amines↗
PubMed1980

Enzymes related to biogenic amine metabolism and personality characteristics in depressed patients.

Levels of the activity of enzyme systems involved in the synthesis and metabolism of biogenic amines have been linked in several reports in the literature with various psychopathological conditions and with variations in personality characteristics. In particular, significant negative correlations have been reported between levels of MAO-activity and sensation seeking. In the present study levels of MAO and DBH-activity were investigated in a series of 30 depressed patients, admitted consecutively, who completed a new personality inventory, the KSP, assumed to measure relatively stable personality traits. Our findings appeared to be consistent with those of earlier authors in that the most pronounced significant (negative) correlation occurred between MAO-activity levels and the monotony avoidance subscale of the KSP. This particular subscale is aimed precisely at measuring thrill-seeking and bears a close relation to the Sensation Seeking Scale used by other authors. In addition a weak positive correlation was found between the same subscale and levels of DBH-activity. Finally a weak negative correlation emerged between levels of MAO and the Guilt subscale of the KSP.

Adolescent↗
PubMed1980

Antagonism of reserpine-induced hypothermia in mice by some beta-adrenoceptor agonists.

The reversal of reserpine-induced hypothermia in mice be three beta-adrenoceptor agonists, terbutaline, salbutamol and clenbuterol, was examined. Terbutaline, 5 and 20 mg/kg intraperitoneally, caused a slight reversal of the hypothermia. Salbutamol, 5 mg/kg intraperitoneally, produced a pronounced and 1 mg/kg a slight reversal. Clenbuterol was very potent in reversing the hypothermic effect of reserpine with significant effect at 0.02 mg/kg intraperitoneally. Propranolol, 2.5 mg/kg intraperitoneally, and the selective beta 2-receptor antagonist IPS 339, 5 mg/kg intraperitoneally, almost completely antagonized the effect of clenbuterol, 1 mg/kg intraperitoneally. The beta-receptor antagonist metoprolol at 5 and 25 mg/kg intraperitoneally only partially antagonized the effect of clenbuterol. Since clenbuterol is much more lipophilic than salbutamol and terbutaline, it is suggested that the reserpine reversal produced by clenbuterol is at least partially of central origin and possibly mediated by stimulation of noradrenergic beta 2-receptors.

Adrenergic beta-Agonists↗
PubMed1980

Anti-aggressive effect of zimelidine in isolated mice.

The anti-aggressive actions of zimelidine, a 5-HT uptake inhibitor, and p-chloroamphetamine (PCA), a 5-HT releasing compound, were examined in isolated male mice. Both agents blocked the aggressive behaviour in a dose range in which they produced inhibition of the accumulation of 14C-5-HT in brain slices. The time course of the inhibition of both compounds was related to their effects on 5-HT mechanisms (5-HT uptake inhibition or 5-HT release) in the brain. These findings suggest that zimelidine and PCA inhibit aggressive behaviour in mice via enhancement of post-synaptic activity in certain 5-HT neuronal pathways. The possible relationship between the role of 5-HT in the anti-aggressive effect and in anxiolytic effects is discussed.

Aggression↗
PubMed1980

Structural requirements for uptake into serotoninergic neurones.

Experiments were performed to examine whether non-hydroxylated tryptamines and 4-chloroamphetamine utilize the membrane 5-hydroxytryptamine carrier to pass into serotoninergic neurones. The accumulation and deamination of 14C-tryptamine by mouse brain slices or homogenates of rat hypothalamus were not inhibited by cocaine or norzimelidine, a selective inhibitor of the neuronal 5-HT uptake. The prevention by alpha-methyltryptamine (10 mg/kg, intraperitoneally), alpha-ethyltryptamine (20 mg/kg intraperitoneally) and 4-chloroamphetamine (20 mg/kg intraperitoneally) of the irreversible inhibtion of monoamine oxidase by pheniprazine (2.5 mg/kg intraperitoneally) and clorgyline (5 mg/kg intraperitoneally) in serotoninergic synaptosomes from mouse brain was not antagonized by pretreatment of the animals with norzimelidine (20 mg/kg intraperitoneally). The partial preventing effect of alpha-ethyl-4-methyl-m-tyramine (H 75/12)(2 X 50 mg/kg intraperitoneally) was, on the other hand, antagonized by norzimelidine. These results do not support the hypothesis that non-hydroxylated tryptamines and 4-chloroamphetamine are transported by the 5-HT carrier.

Animals↗
PubMed1980

Serum dopamine-beta-hydroxylase and the augmenting-reducing response.

In 84 consecutively admitted inpatients, as well as in 7 healthy volunteers, visual evoked potential to stimuli of varying intensities and serum DBH activity were determined. Patients with an augmenting (Aug.) response, i.e., a tendency to enlarge the perception of stimulation, were found to have the lowest serum DBH activities. As Aug. patients have earlier been shown to have low levels of HVA in CSF, indicating a low turnover in the dopaminergic systems in the CNS, the results indicate that the genetic factor determining the serum DBH activity may in some way also reflect the dopaminergic turnover in CNS.

Adult↗
PubMed1979

Acute effects of zimelidine and alaproclate, two inhibitors of serotonin uptake, on neuroendocrine function.

The accumulation of 14C-5-hydroxytryptamine in human platelets in vitro and plasma levels of a number of hypophyseal hormones and cortisol in healthy male volunteers were determined after acute oral administration of zimelidine and alaproclate, two selective inhibitors of serotonin (5-HT) uptake. Alaproclate (100 mg) significantly inhibited the accumulation of 14C-5-HT by 42% at 90 minutes but showed no significant effect at 4 hours. At 200 mg the decrease in the accumulation was 55% after 90 minutes and 31% after 4 hours. Zimelidine (200 mg) caused a 72% decrease at 90 minutes and 73% at 4 hours. Plasma levels of prolactin, growth hormone, luteinizing hormone, follicle stimulating hormone, and thyroid stimulating hormone remained unchanged after zimelidine and alaproclate, and the levels were comparable to those after placebo. A physiological decline of plasma cortisol levels was noted in the morning during the test period of 4 hours, but there were slight differences in the secretory pattern after the different drugs used.

Adult↗
PubMed1979

Forebrain projections of the ventral tegmentum as studied by axonal transport of [3H]dopamine in the rat.

Twenty-four hours after [3H]dopamine ([3H]DA) injections into different parts of the ventral tegmentum the radioactivity recovered in the forebrain showed a highly regional distribution which corresponded to well-known DA projections. Selective degeneration of DA-neurons with 6-hydroxydopamine (6-OHDA) markedly reduced the axoplasmic transport after [3H]DA injections. The ventral tegmental area (VTA) was found to project primarily to the nucleus accumbens, olfactory tubercle and amygdala. The DA-innervation of the entorhinal cortex and the amygdala derive from cells widely distributed in the VTA and SN.

Animals↗
PubMed1979

Platelet monoamine oxidase in a pedigree with schizophrenia: an interlaboratory project.

Conflicting reports on the association between platelet MAO activity and schizophrenia prompted a critical review and determinations on identical samples at one laboratory in Sweden and one in the U.S.A. Samples originated from eight schizophrenics and 27 relatives belonging to a large pedigree, thus ensuring biological homogeneity. In the USA laboratory, a significantly lower MAO activity was found in the schizophrenics when benzylamine or beta-phenylethylamine was used as substrate (but not with tryptamine), while a similar result was obtained in the Swedish laboratory when tryptamine was used (but not with benzylamine or beta-phenylethylamine). Comparisons between materials examined in different laboratories do not seem meaningful until differences in methodologies have been clarified. At present there is neither proof nor disproof of MAO being a "genetic marker" for vulnerability to the schizophrenic disorder.

Benzyl Compounds↗
PubMed1979

Inhibition of 3H-dopamine accumulation in reserpinized and normal rat striatum.

The inhibitory potencies of 27 compounds on the accumulation of 3H-dopamine (DA) in synaptosome-rich striatal homogenates of normal and reserpinized rats were determined. It was found that some compounds, e.g. amphetamine derivatives, phenmetrazine, phenethylamine derivatives and tryptamine derivatives were considerably more potent in the reserpinized preparation than in the normal one. Other compounds, e.g. amfonelic acid, mazindol, EXP 561, benztropine, pipradrol, nomifensine, methylphenidate and cocaine had similar potencies in the two preparations. It is suggested that the compounds enhanced by reserpine are more potent as DA releasing agents than as inhibitors of the DA uptake, whereas the compounds in the other group are most potent as uptake inhibitors. Interestingly, these two groups completely agree with the two groups of central stimulatory agents, viz. the amphetamine-like and the methylphenidate-like drugs.

Amphetamines↗
PubMed1979

Release of 3H-noradrenaline from the rat vas deferens under various in vitro conditions.

The release of 3H-(-)-noradrenaline (NA) from rat vas deferens in vitro was examined under various experimental conditions. It was found that in normal and reserpinized vas deferens the release of NA evoked by (+)-amphetamine (5 X 10(-6) M) or low external Na+ (26 mM) was antagonized by imipramine methiodide and desipramine, inhibitors of the NA uptake, but was not dependent on the presence of Ca2+ in the medium and was not antagonized by the potent local anaesthetic agent bethoxycaine. The release evoked by veratridine in reserpinized tissue was antagonized by the uptake inhibitors but was in normal tissue only partially inhibited in presence of Ca2+ but almost completely in absence of Ca2+. The release by high K+ (117 mM)+low Na+ (26 mM) in normal tissue was dependent on the presence of Ca2+ and was antagonized by the muscarinic agonists carbacholine and metacholine and by high concentrations of desipramine. In the reserpinized vasa the corresponding release was not dependent on Ca2+ and was not antagonized by the muscarinic agents but was inhibited by high concentrations of desipramine.

Aminobenzoates↗