Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of dopamine on the sensory discharges originating from arterial chemo- and baroreceptors were studied in vitro using carotid bodies or sinuses excised from anaesthetized cats and superfused with Locke's solution. 2. Intrastream injections of dopamine 10-200 mug produced a transient depression of the frequency of chemoreceptor discharges. This effect was observed in response to the first injection in eighteen out of twenty preparations. 3. The inhibitory effect of dopamine can counteract partially or totally the excitation of chemoreceptors evoked by simultaneous application of acetylcholine or cyanide. 4. This inhibitory effect of dopamine is reduced or abolished by pretreatment with dopaminergic (Spiroperidol) or alpha-adrenergic (Dibenamine) blockers. 5. In response to repeated injections of dopamine applied at short intervals, the inhibitory effect is replaced by a biphasic effect (early inhibition followed by late excitation), a late and long-lasting excitation or no changes in chemoreceptor activity. The late excitatory effects of dopamine are not blocked by dopaminergic or alpha-adrenergic blockers. 6. Noradrenaline does not affect the chemoreceptor activity of the superfused carotid body. DL-DOPA induces only a late and long-lasting excitatory effect. 7. In carotid sinus preparations, dopamine induces a weak but long-lasting increase in the frequency of baroreceptor discharges. 8. It is concluded that dopamine may play a modulatory role in the generation of chemoreceptor activity through local regulatory processes.
 ...
PMID:Effects of dopamine on carotid chemo- and baroreceptors in vitro. 23 40

A strategy is presented for biological psychosis research with neuroleptics acting as a point of crystallisation like antidepressants do in biological depression research. The neuroleptics chlorpromazine, haloperidol and oxypertine were studied, and it was found that they influence central catecholamine (CA) metabolism in man. An increased central dopamine (DA) turnover was found to occur in psychotic disorders, mostly in the form of motor agitation. As the first of a planned series of studies, chlorpromazine with presumed ability to reduce both DA-ergic and noradrenaline (NA)-ergic transmission and oxypertine as a more selective blocker of NA-ergic transmission were selected for comparison. The overall therapeutic effect of oxypertine was inferior to that of chlorpromazine, whereas oxypertine proved more effective in cases where loss of initiative was predominant. On the other hand, chlorpromazine exerted a more marked influence on extrapyramidal motor functions than oxypertine. In chronic psychotic disorders with inertia, oxypertine thus seems to be a neuroleptic which is strong enough to prevent exacerbation of delusions and hallucinations while at the same time increasing the level of motivation. These findings were in accordance with our predictions. The comparative study is illustrative of the practical significance of the research approach in this study: The biochemical action profile of a neuroleptic seems to be a more reliable indicator of its clinical action than does its chemical structure.
 ...
PMID:Biochemical research into psychosis. 23 63

From the serial studies on imipramine dependent noradrenaline (NA) rise at different values of gastric acid with 336 registrations of blood pressure, it follows that a lawful relation exists between imipramine absorption and gastric juice acidity. At pH values of 3.5--6.0 a distinct decreased absorption of orally supplied imipramine was stated. After changing the pH value by acid substitution, a full absorption is reached. This state seems to be of special practical importance in the treatment of depression with thymoleptics.
 ...
PMID:[Changes in imipramine induced noradrenaline potentiation by varying activity of gastric juice under oral medication]. 23 41

The aim of the study was to quantitatively compare the relative affinities of noradrenaline, adrenaline, dopamine and isoprenaline for the, probably neural, receptors mediating feedback control of sympathetic neurotransmitter secretion. The experiments were carried out in isolated superfused field stimulated guinea-pig vas deferens, in which the noradrenaline stores had been labelled by preincubation with tritiated (-)-noradrenaline. Desipramine and normetanephrine were added to prevent rebinding of transmitter. Exogenous noradrenaline was found to cause a dose-dependent and reversible depression of the secretion of tracer noradrenaline evoked by field stimulation. Since the depressing effect was not affected by a ten-fold rise in the desipramine concentration, it seems likely that it was not due to uptake and preferential secretion of unlabelled exogenous noradrenaline, but was truly due to depression of the secretory mechanism. Adrenaline was significantly more potent than noradrenaline, as inhibitor of the secretion of tracer transmitter, while dopamine, at the same molar concentration, was without effect. The beta-agonist isoprenaline did not depress, but rather tended to enhance, the secretion of tracer noradrenaline. It is concluded that the receptors controlling the secretion of noradrenaline from the sympathetic nerves of guinea-pig vas deferens quantitatively-with regard to sensitivity-as well as qualitatively-with regard to order of preference for different catecholamines-resemble the "classical" alpha-receptors of e.g. smooth muscle in the same tissue.
 ...
PMID:Selectivity for catecholamines of presynaptic alpha-receptors involved in feedback control of sympathetic neurotransmitter secretion in guinea-pig vas deferens. 24 Jan 32

1 An electrophysiological study has been made of the effects of either blocking noradrenaline (NA) uptake or alpha-adrenoceptors on conduction in adrenergic preterminal axons and on NA release. 2 The excitatory junction potential (e.j.p.) evoked by a single stimulus increased slightly in duration (maximum 20%) in the presence of high concentrations of desipramine or cocaine (larger than or equal to 1 mug/ml) but there was no change in the spontaneous miniature excitatory junction potential (m.e.j.p.s); the single compound preterminal action potential was decreased in amplitude by a maximum of 10%. The e.j.p., m.e.j.p. and the terminal action potential were not altered by lower concentrations of these drugs (less than mug/ml). 3 The increased decline of the e.j.p. amplitude observed during the first few hundred impulses at high frequencies (10 Hz) in the presence of desipramine or cocaine was accompanied by a similar decline in the amplitude of the preterminal compound action potential, suggesting that the latter gave rise to the former. 4 These observations suggest that the action on post-synaptic alpha-adrenoceptors of NA released by single impulses is terminated by diffusion, and that any NA which is subsequently taken up into nerves is metabolized. 5 All the alpha-adrenoceptor blocking drugs tested reversed the normal depression in e.j.p. amplitude observed during the first few hundred impulses at high frequencies to facilitation; this was unaccompanied by any changes in the preterminal compound action potential. 6 Alpha-Adrenoceptor blocking drugs did not alter the potentiating effect which a conditioning impulse had on the amplitude of the e.j.p. evoked by a subsequent test impulse. The facilitated release of NA during trains of impulses was quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 7 It is suggested that if there is an auto-inhibition of NA release, then it is unlikely that the pre- and post-synaptic alpha-adrenoceptors are identical.
 ...
PMID:An electrophysiological analysis of the effects of amine-uptake blockers and alpha-adrenoceptor blockers on adrenergic neuromuscular transmission. 24 45

Cerebral ischemia was induced in normothermic, artificially ventilated rats, anesthetized with 70% N2O or 150 mg/kg of phenobarbitone, by bilateral occlusion of the common carotid arteries and by simultaneous depression of the mean arterial blood pressure to 50 mm Hg. The levels of tyrosine, dopamine (DA), noradrenaline (NA), tryptophan, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were measured after 15 min of ischemia as well as after 30 min of recirculation. In separate experiments (70% N2O) the rate of accumulation of DOPA and 5-hydroxytryptophan (5-HTP) was determined in three different brain regions (striatum, limbic forebrain and hemispheres) during recirculation. During ischemia, the monoamine pattern was unaffected. Following recirculation, increases in DA, 5-HIAA, tyrosine and tryptophan were found irrespective of the type of anesthesia used. Pronounced postischemic decreases in NA and 5-HT were observed in animals anesthetized with nitrous oxide but not in those given phenobarbitone. During recirculation the rate of tyrosine hydroxylation increased in all three brain regions while tryptophan hydroxylation was reduced. It is tentatively concluded that following transient, global cerebral ischemia, neuronal activity is low or eliminated in dopaminergic and serotoninergic neurons and high in noradrenergic neurons.
 ...
PMID:Influence of transient ischemia on monoamine metabolism in the rat brain during nitrous oxide and phenobarbitone anaesthesia. 30 81

1 Stereotaxic lesioning and microiontophoretic techniques were used to study the effects of lesions of the medial forebrain bundle (MFB) on the potentiation by antidepressant drugs of responses to monoamines of cortical neurones.2 Active uptake of noradrenaline (NA) and 5 hydroxytryptamine (5-HT) by synaptosomes from the motor and somatosensory cortex was reduced to approximately 20%, 10 to 14 days following lesion of the MFB in rats.3 Unilateral lesions of the MFB caused changes in responsiveness of neurones to NA and 5-HT, applied by iontophoresis, in the cortex ipsilateral to the lesion. Excitatory responses to both amines were observed less frequently and depression was the predominant response. Excitatory responses on the lesioned side were significantly smaller than on the unlesioned side, but the size of depressant responses was unaltered.4 Viloxazine strongly potentiated responses of cortical neurones to NA and 5-HT on both sides of the brain of MFB-lesioned rats. There were no significant differences in the potentiation of responses to monoamines on the lesioned or unlesioned sides of the brain.5 Desipramine potentiated responses to NA of neurones in the cortex ipsilateral to MFB lesions.6 Chlorimipramine potentiated responses to 5-HT of neurones in the cortex ipsilateral to MFB lesions.7 It is concluded that antidepressants can potentiate responses to monoamines despite a profound reduction in presynaptic terminals. The potentiation is unlikely to be the result of blockade of monoamine uptake into presynaptic terminals, and is probably a postsynaptic effect of the antidepressant drugs.
 ...
PMID:Potentiation of responses to monoamines by antidepressants after destruction of monoamine afferents. 31 65

Lofepramine, an imipramine analogue, was compared with imipramine in a multicentre, double-blind clinical trial. The 62 patients (31 in each of two treatment groups) had a depressive syndrome that normally would have been treated with a tricyclic antidepressant. These patients had not received any adequate treatment for this present depressive episode. After a wash-out period and once a week during treatment (up to 5 weeks), routine laboratory tests and electrocardiograms was done. The dosage was 50 mg t.i.d. for imipramine and 70 mg t.i.d. for lofepramine. Depression ratings with the Cronholm-Ottosson depression rating scale were performed before treatment and once weekly for 3 weeks and then in the 5th week. The last four ratings were combined with rating of side-effects. In the 5th week of treatment 15 out of 31 in the lofepramine group and 18 out of 31 in the imipramine group had recovered. This difference was not significant, nor did the median values of individual symptoms differ between the groups. The side-effects were moderate and the two groups only differed significantly in the items "dry mouth" and accommodation disturbances in favour of lofepramine. The drug compliance was checked by plasma levels of desmethylimipramine in the imipramine group, parent compound, and "apparent" desmethylimipramine in the lofepramine group. The relationship between plasma drug levels, the effect on noradrenaline uptake in vitro and amelioration discussed in Siwers et al. (1977) in this issue. The clinical outcome in the two groups did not differ significantly; interpretation of this result is discussed in relation to the reliability and selection of patients.
 ...
PMID:Comparative clinical evaluation of lofepramine and imipramine. Psychiatric aspects. 32 Aug 27

A multicentre comparative clinical evaluation of lofepramine, an imipramine analogue, and imipramine has been made with double-blind technique and fixed dosage (lofepramine 70 mg t.i.d., imipramine 50 mg t.i.d.). Plasma was drawn after 3 weeks for determination of noradrenaline-uptake inhibitory capacity of the parent compound and/or its active metabolites. Plasma concentrations of lofepramine and desmethylimipramine (DMI) were determined in the same samples. The concentrations of lofepramine in the whole material were low (5-27 ng/ml) except for one patient who had a level of 53 ng/ml. In both groups of patients there was an almost 40-fold range in the plasma levels of DMI or apparent DMI. The patients were rated for severity of depression before treatment, then once weekly for 3 weeks and finally during the fifth week. For further information concerning the psychiatric aspects, see d'Elia et al. in this issue (1977). A significant correlation was found between the concentrations of DMI and the noradrenaline-uptake inhibitory capacity in the plasma samples. No correlations were found between uptake inhibitory capacity of plasma samples and the amelioration scores.
 ...
PMID:Comparative clinical evaluation of lofepramine and imipramine. Pharmacological aspects. 32 Aug 28

1. An investigation was carried out into the mechanism of unexplained hypotension in patients with fulminant hepatic failure. The cardiac output and peripheral resistance were compared in normotensive and hypotensive patients. In addition, the serum concentration of the false neurotransmitter octopamine and the pressor response to noradrenaline, and to the indirectly acting sympathomimetic agent tyramine, were measured in hypotensive and normotensive patients with fulminant hepatic failure and in healthy subjects. 2. The cardiac output and the peripheral resistance were decreased in the hypotensive patients, and their mean heart rate was slower than in the normotensive patients. Although the serum octopamine concentration was significantly elevated in the patients compared with the control subjects, the highest octopamine concentrations were unexpectedly found in the normotensive patients and a significant positive correlation could be demonstrated between the resting blood pressure and the serum octopamine concentration. The pressor response to tyramine and noradrenaline were similar in the hypotensive patients, the normotensive patients and control subjects. 3. These results suggest that neither increased serum concentrations of the false neurotransmitter octopamine, nor end-organ insensitivity to released noradrenaline are responsible for the hypotension. A more likely explanation is toxic depression of the vasomotor centre. The opening of peripheral arteriovenous shunts, possibly as a result of endotoxaemia, might be an additional factor.
 ...
PMID:The role of the false neurotransmitter octopamine in the hypotension of fulminant hepatic failure. 32 Nov 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>