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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.
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PMID:Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects. 1 May 83

A relationship between brain monamines and endogenous depression is suggested by observations on the mode of action of drugs producing or alleviating depressive symptoms. For example, reserpine is capable of faithfully mimicking the clinical picture of endogenous depression, which may be related to monoamine depletion. On the other hand, antidepressant drugs, e.g. the monoamine oxidase inhibitors, the tricyclic antidepressants and the monoamine precursors appear to increase the availability of monoamines at postsynaptic receptor sites. The different classes of antidepressant agents in general appear to potentiate each other's actions, according to animal data and clinical observations. Studies on the mode of action of tricyclic antidepressants with different profiles and on monoamine precursors suggest that 5-hydroxytryptamine is primarily involved in the control of mood, and noradrenaline in psychomotor activity. Clincial investigations initiated by the drug studies have demonstrated changes in monoamine metabolism in endogenous depression. The available evidence thus suggests a causal relationship between disturbances in monoamine metabolism and depression.
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PMID:The contribution of drug research to investigating the nature of endogenous depression. 1 May 84

The effect of adrenergic blockade on gastric secretion altered by catecholamines was studied for 4 hr after injection in rats with chronic gastric fistulas. The alpha-adrenergic blockers phenoxybenzamine and phentolamine significantly inhibited the basal secretion of HCl and pepsin. Blockade of the beta-adrenergic receptors with propranolol did not change this secretion. Practolol in small doses slightly increased and in larger doses inhibited HCl out-put. Of the catecholamines, adrenaline and dopamine most markedly reduced HCl and pepsin secretion, while noradrenaline and isoprenaline had a weaker effect. Neither alpha- nor beta-adrenergic blockers prevented the inhibitory action of the catecholamines employed, but intensified the depression of the gastric secretion provoked by them. Adrenergic blockers inhibited secretion after catecholamines as well as basal secretion. This indicates that these two antagonistic groups of compounds act independently on the mechanism controlling gastric secretion. It is unlikely that this takes place indirectly through changes in the blood supply of the gastric mucosa.
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PMID:Effect of adrenergic blockade on gastric secretion altered by catecholamines in rats. 1 61

The nociceptive reflex activity and analgesic effect of morphine were studied in rats using the hind paw stimulation test. The stimulation threshold was significantly increased in animals with bilateral destruction of the locus coeruleus (LC), and was reduced after lesion of the dorsal raphe nucleus (DR). LC lesions produced a selective lowering of noradrenaline (NA) content in the forebrain, while DR lesions resulted in a reduction in serotonin levels. Lesioning both LC and DR significantly reduced both NA and serotonin contents even when the stimulation threshold was not altered. Morphine produced a significant and dose-dependent elevation of the stimulation threshold in sham-operated animals, while morphine analgesia was almost completely inhibited by destruction of LC, DR and both the nuclei. These results imply that a depression of LC-mediated noradrenergic tone results in a decreased sensitivity to painful stimuli, whereas a reduction of raphe-derived serotonergic tone produces the opposite effect against LC. It is suggested, however, that both of these monoamines from the LC and DR are necessary for the analgesic effect of morphine.
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PMID:Attenuation of morphine analgesia in rats with lesions of the locus coeruleus and dorsal raphe nucleus. 1 37

Subtetanic contractions of the guinea-pig isolated soleus, a slow-contracting skeletal muscle, were evoked by transmural field-stimulation. Isoprenaline caused a dose-dependent depression of the contractions. This effect was inhibited by propranolol and H 35/25 (1-(p-tolyl-2-isopropylamino-1-propanol) but not by practolol. Similar results were obtained for terbutaline. Tazolol and H 80/62 (1-isopropylamino-3-(p-hydroxyphenoxy)-2-propanol (HCl), selective beta1-agonists, had no effect per se but inhibited the effect of terbutaline. Adrenaline, noradrenaline, and dopamine all caused a dose-dependent decrease in the force of the soleus contractions, their potencies being in that order. Tyramine did not appreciably affect the contractions nor did it inhibit the effect of terbutaline. Pretreatment with reserpine, if anything, increased the response to terbutaline. It is concluded, in conformity with previous in vivo studies, that the adrenergic receptor mediating the effect on the soleus muscle contractions is of the beta2-type. Indirect sympathomimetic effects do not contribute to the responses observed on the isolated soleus muscle.
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PMID:Analysis of the beta-receptor mediated effect on slow-contracting skeletal muscle in vitro. 2 Dec 60

1 Histamine produced a dose-dependent contraction of the isolated portal vein of the rabbit. This contraction was not antagonized by atropine, methysergide, indomethacin, cocaine or 6-hydroxy-dopamine, nor by pretreatment of the rabbit with reserpine. 2 The response to histamine was blocked by H1-receptor antagonists only when the blocking agent was used in very high concentrations, and was not antagonized by the H2-receptor blocking agent, metiamide, H1-receptor antagonists did not block the effects of 5-hydroxytryptamine. 3 The contractions elicited by histamine, 5-hydroxytryptamine and noradrenaline were blocked by phentolamine. 4 Desensitization to high doses of 5-hydroxytryptamine caused a concomitant depression in the response to histamine but not to noradrenaline or acetylcholine. 5 The results suggest that the contractions of rabbit portal vein elicited by histamine are not mediated by receptors of the H1- or the H2-type, but may involve an action of histamine at a receptor which is also involved in the action of 5-hydroxytryptamine.
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PMID:Responses of rabbit portal vein to histamine. 2 80

The influence of mainly alpha-adrenergic drugs (noradrenaline, adrenaline, phenylephrine), indirect sympathomimetics (ephedrine, tyramin) and dopamine on the exocrine pancreatic function of the isolated perfused organ of cats was studied. The injection of noradrenaline and adrenaline induced simultaneously a rapid depression of flow rate and an increase of perfusion pressure. Phenylephrine, indirect sympathomimetic drugs and dopamine did not change the perfusion pressure and the hydrelatic function (flow rate, secretion of chloride and total calcium). The protein and enzyme secretion was enhanced both in normal animals and cats pretreated by reserpine or 6-hydroxydopamine. The pancreatic protein secretion was inhibited by alpha-adrenolytic as well as beta-adrenolytic substances, tetracain and atropine. It is concluded, that mainly alpha-adrenergic drugs stimulate the pancreatic enzyme secretion in a cholinergic manner.
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PMID:[The effect of mainly alpha-adrenergic drugs, indirect sympathomimetrics and dopamine on exocrine pancreatic function. Studies in the isolated cat pancreas (author's transl)]. 2 65

The experiments reported here investigated the effect of chlorpromazine (CPZ) alone or after inhibition of catecholamine (CA) synthesis on paradoxical sleep (PS) in the rat. The dose--response curve for CPZ was biphasic with enhancement of PS after low doses, and depression of PS after higher doses. In contrast, low doses of CPZ after inhibition of CA synthesis markedly decreased PS. This decrease was greater after tyrosine hydroxylase inhibition than after dopamine-beta-hydroxylase inhibition. These results support the view that low doses of CPZ produce increased activity in brain CA synapses, and that both dopamine and noradrenaline participate in the control of PS in the rat.
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PMID:Biphasic effect of chlorpromazine on rat paradoxical sleep: a study of dose-related mechanisms. 2 79

Intracellular injections of noradrenaline or dopamine in spinal motoneurones of cats have a clear depolarizing action associated with particularly marked depression of spike potentials and their after-hyperpolarization, but with little slowing-down of the falling phase of the action potential. These effects are associated with an increase in input resistance, and they are reversible and reproducible in the same neurone. Intracellular injections of 5-hydroxytryptamine have some depolarizing action and increased input resistance, but they produced no comparable depression of the action potential and tended to enhance the after-potentials and increase excitability. It is concluded that changes in intracellular levels of monoamines, whether physiological or drug induced, may be of significance for central neuronal function.
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PMID:Intracellular actions of monoamine transmitters. 3 May 29

The author goes briefly over the metabolism of the main cerebral monoamines, the functioning of synapses, as well as the methods used in studying the biochemistry of depression. Beyond all existing contradictory results, a review of the main works in this field enables us to point out some leading ideas:--Depression would be due to and/or accompanied by a monoaminergic deficiency: some authors emphasize the serotonin one, others the noradrenaline one.--The regulation of mood most probably finds its origin in the monoaminergic balance, rather than in the gross rates of any particular monoamine.--Disturbances are to be found on all metabolic levels: monoaminergic, hydroelectrolytic, hormonal, glucidic, lipidic, lipidic... Close intrication exists between those different metabolisms.--The interaction between the different aminergic systems and the metabolic ways, as well as the dispersion of the acknowledged results, impose more and more the necessity of a biochemical typology of depression, which would lead to a predictive approach to the evolution and treatment of depressive illness.
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PMID:[Biochemistry of depression. Literature analysis]. 3 Jun 16


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