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

The effects on GH and PRL secretion of several pharmacological agents known to modify central neurotransmitter action were determined in unanesthetized male rats. Phenoxybenzamine, an alpha-adrenergic blocker (5 mg/kg iv), abolished episodic GH secretion and caused elevation of serum PRL levels. Propranolol, a beta-adrenergic blocker (5 mg/kg iv), had no effect on GH secretion and caused a small but significant depression in PRL levels. Parachlorophenylalanine methyl ester, an inhibitor of tryptophan hydroxylase (300-350 mg/kg ip), resulted in significant inhibition of GH pulsatile secretion and suppressed PRL levels. Methysergide hydrogen maleinate (25 mg/kg iv), a serotonin receptor antagonist, also inhibited GH secretion, but produced a transient stimulation in PRL levels. Atropine sulfate (2 mg/kg iv) caused significant suppression in GH secretion, but had no effect on PRL. Picrotoxin, a gamma-aminobutyric acid antagonist, in a subconvulsive dose of 1-3 mg/kg iv, also depressed GH episodic secretion but did not affect PRL levels. These results indicate that several neurotransmitters, i.e., norepinephrine, serotonin, acetylcholine, and gamma-aminobutyric acid, found in high concentration in the hypothalamus, influence GH and PRL secretion.
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PMID:Neuropharmacological regulation of episodic growth hormone and prolactin secretion in the rat. 3 92

The interaction between (--)-cocaine and responses to 5-HT elicited through serotonin receptors on autonomic neurones has been investigated on the rabbit heart and the guinea-pig ileum. Low concentrations of (--)-cocaine or its stereoisomer, (4)-pseudococaine, produced shifts to the right of the 5-HT dose-response curves on heart and ileum with no depression of the maximum responses to electrical stimulation or dimethylphenylpiperazinium remained unaffected. A Schild analysis of data obtained on heart and ileum indicated competitive antagonism of 5-HT by (--)-cocaine. Antagonism of 5-HT by the cocaine isomers cannot be ascribed to local anaesthesia per se since neither lignocaine, tetracaine, benzocaine nor bu tacaine were selective antagonists of 5-HT. Similarly, inhibition of monoamine uptake seems of minimal relevance since desipramine proved only a weak antagonist of 5-HT on the heart and did not influence the 5-HT antagonist potency of (--)-cocaine. Selective blockade of 5-HT neuronal responses is a property shared by several structural analogues of (--)-cocaine and (+)-pseudococaine; nor-(--)-cocaine proved the most potent of these, being active at a concentration of 2 x 10(-8) M. These data indicate that (--)-cocaine and several of its derivatives inhibit 5-HT stimulation of both adrenergic and cholinergic autonomic neurones through competition with the agonist at serotonin receptor sties. Since morphine, the tool normally used to identify responses mediated through neuronal serotonin receptors, acts only at certain "morphine-sensitive" junctions and then, non-discriminately, the cocaine analogues, and particularly nor-(--)-cocaine would seem to offer real advantages as tools for differentiating such responses.
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PMID:Blockade of serotonin receptors on autonomic neurones by (-)-cocaine and some related compounds. 52 45

Intraventricular administration of serotonin to rats causes 'wet-dog' shakes, a sign of morphine withdrawal. The frequency of shakes is dose-dependent. Shaking is potentiated by pretreatment with an inhibitor of monoamine oxidase or with 5,7-dihydroxytryptamine, and is depressed by morphine or serotonin receptor blockers. Depression of serotonin-induced shaking by morphine is reversed rapidly by naloxone. However, naloxone did not reverse the inhibition of 'wet-dog' shakes caused by serotonin receptor blockers.
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PMID:Effect of morphine on 'wet-dog' shakes caused by cerebroventricular injection of serotonin. 57 8

The selective serotonin reuptake inhibitors (SSRIs) are a tribute to the ingenuity of pharmacologists and designers of molecules. Not only do these drugs have remarkable selectivity for the reuptake of serotonin compared with other monoamines, but also they have a commendable lack of affinity for receptors including the serotonin receptor. In contrast, the classical tricyclic antidepressants (TCAs) are less specific in their pharmacological action. In addition to inhibiting the reuptake of serotonin, TCAs inhibit the uptake of noradrenaline, dopamine and tyramine, and antagonize cholinergic (muscarinic), adrenergic and histaminergic receptors. Moreover, TCAs have quinidine-like anti-arrhythmic activity and lower the seizure threshold. Clinical investigations have shown that the SSRIs have equivalent therapeutic efficacy compared with the TCAs in the treatment of depression. However, the pharmacological specificity of the SSRIs is a clinical advantage since they lack the propensity to cause dry mouth, blurred vision, urinary hesitancy, constipation, hypotension and arrhythmia. Furthermore, the SSRIs are relatively safe in overdosage. The similarities between the SSRIs are more obvious than their differences: all are highly potent and selective inhibitors of serotonin reuptake with efficacy in the treatment of depression. Nevertheless, each has a distinctive pharmacological profile. In this review the characteristics desired in an "ideal" antidepressant are examined, and the ways in which the TCAs and SSRIs fit this ideal are compared.
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PMID:Clinical implications of the pharmacology of serotonin reuptake inhibitors. 148 74

The past decade has seen important progress in understanding the localization, pharmacology, and function of serotonin (5-HT) receptor subtypes. At least seven subclasses have been shown to exist, and evidence is emerging to suggest further subclassification. Serotonin is involved in numerous physiological processes (e.g. feeding, sleep, pain, sexual behavior, temperature regulation) and pathophysiological ones. Serotonin reuptake blockers have been found effective in the alleviation of depression and attacks of panic, and are at varying stages of clinical evaluation in the treatment of obsessive compulsive disorder, chronic pain, and bulimia nervosa. Selective potent serotonin receptor agonists and antagonists show promise in the treatment of migraine, nausea and vomiting, schizophrenia, anxiety, hypertension, and Raynaud's disease.
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PMID:[New therapeutic possibilities with drugs affecting serotonin receptors]. 150 27

Serotonin basic neuroscience discoveries are evolving at a very fast pace and are leading to innovations in clinical psychiatry and in drug development. Numerous novel pharmacological tools, each selective for a given serotonin receptor subtype, are being applied to several psychiatric disorders. The strategy employed is theory driven and hypothesis oriented, aiming for new drug development that selectively targets receptors that are rational sites for therapeutic actions. Thus, serotonin uptake inhibitors are targeting not only depression, but also obsessive-compulsive disorder (OCD). Serotonin1A agonists are targeting not only depression and anxiety, but also mixed anxiety depression. These and other agents selective for additional receptors are being tested in impulse control disorders; eating disorders; addictive disorders; and aggressive, violent, self-destructive, and suicidal behaviors. Serotonin research is an excellent example of how basic science discoveries in the 1990's "Decade of the Brain" are resulting in important advances in therapeutics for psychiatry.
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PMID:Serotonin neuroscience discoveries usher in a new era of novel drug therapies for psychiatry. 160 40

Thirty-three years ago, Gaddum and Picarelli classified the serotonin receptors in the guinea pig ileum into D and M types based on the activity of dibenzyline and morphine to block contractions of intestinal smooth muscle caused by serotonin. The subsequent location of specific ligand binding sites for serotonin in the brain has led to the identification of at least eight serotonin receptor sub-types in rat brain. While there is some controversy over the functional importance of many of these receptor sub-types, there is evidence that they fall into two major groups according to the nature of their coupling to secondary messengers or ion channels. Thus the 5-HT1 and 5-HT2 receptors appear to occupy the G protein receptor sub-family which may be coupled either to adenylate cyclase (most 5-HT1 sub-types) or phosphatidyl inositol (5-HT2 sub-types). The central "M" receptors (now termed 5-HT3) appear to occupy a ligand gated ion channel super-family. The cloning of three of the serotonin receptor sub-types in 1989 (5-HT1A, 5-HT1C and 5-HT2) has been of importance in enabling the receptor sub-types to be classified as specific protein molecules encoded by specific genes. The problem now arises with regard to the linking of the changes in the cellular activity of the various receptor sub-types with the plethora of behavioural changes that arise as a consequence of the actions of serotonin in the brain. The present review summarizes the evidence implicating the role of specific serotonin receptor sub-types in eating disorders, sleep, sexual activity, anxiety states, aggression, schizophrenia and depression. A summary of the relationship between these receptor sub-types and their possible involvement in the aetiology of these diseases is shown in Table 2.
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PMID:Sub-types of serotonin receptors: biochemical changes and pharmacological consequences. 162 53

Several developments in serotonin neuropharmacology have implications for psychiatric disorders and have already begun to impact their treatment. Selective inhibitors of serotonin uptake, which enhance serotonergic function by preventing the removal of serotonin from the synaptic cleft via the membrane transporter, have been introduced for the treatment of depression and may be effective in other disorders. Precursor loading can increase serotonin concentrations in the synaptic cleft, and tryptophan--which has been available in health food stores and drug stores--had become increasingly used for self-medication of depression, insomnia, and premenstrual syndrome. Conversion to serotonin is not the major metabolic pathway for tryptophan, and large increases in other tryptophan metabolites (such as quinolinic acid, a substance that is excitotoxic at high concentrations) accompany small increases in extracellular serotonin. The recent epidemic of the eosinophilia-myalgia syndrome associated with tryptophan now appears due to a trace contaminant in the product from a single manufacturer. A major advance in serotonin pharmacology has been the elucidation of serotonin receptor heterogeneity. At least seven receptor subtypes (5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2, 5-HT3, 5-HT4) have been identified in brain. Direct-acting agonists and antagonists can have selective affinity for specific receptor subtypes. Selective activation of 5-HT1A receptors seems to cause anxiolytic and possibly antidepressive effects. Selective antagonists of 5-HT2 or 5-HT3 receptors may be useful in treating anxiety and schizophrenia. Drugs that enhance serotonergic function suppress aggression in animals, but the specific receptor subtypes involved are not known. The advances being made in serotonin pharmacology will help define the role of this brain neurotransmitter in psychiatric and other disorders and can be expected to lead to further therapeutic advances.
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PMID:Role of serotonin in therapy of depression and related disorders. 167 51

The current hypersensitive postsynaptic serotonin receptor theory of depression developed and expanded by Aprison and Hingtgen was based on an animal model of behavior in which food-reinforced approach behavior was suppressed following 5-hydroxytryptophan (5-HTP) administration. In this paper, data are presented to show that when the same animal is taught to emit, alternatingly, approach and avoidance behavior, and the serotonin precursor, 5-HTP, is administered, only the approach behavior is affected. Adult, male Wistar rats were trained on Sidman avoidance (RS20:SS10) and food-reinforced approach (VI 1) schedules. During the first part of this study, rats received separately 50-min sessions for approach and avoidance responding. For the second part, both schedules were given in the same experimental chamber. In the third part, 10-min alternating approach and avoidance components were combined in the same 50-min sessions. Significant behavioral suppression of approach responding was observed following administration of L-5-HTP (50 mg/kg IP), as well as after D,L-5-HTP (25 and 50 mg/kg IP) in a dose-dependent relationship, whereas no significant effect was seen for Sidman avoidance responding during this type of session. These results support the role of serotonin in food-reinforced approach behavior and suggest that suppression of Sidman avoidance behavior may be mediated by other neurotransmitter systems.
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PMID:Differential effect of 5-hydroxytryptophan on approach and avoidance behavior in rats. 201 45

To evaluate whether serotonin reuptake inhibition is critical to the treatment of obsessive-compulsive disorder, 40 outpatients with a principal diagnosis of obsessive-compulsive disorder were randomized in a double-blind fashion to 8 weeks of treatment with either the serotonin reuptake inhibitor fluvoxamine maleate (n = 21) or the norepinephrine reuptake inhibitor desipramine hydrochloride (n = 19). Fluvoxamine was significantly better than desipramine in reducing the severity of obsessive-compulsive symptoms, as measured by the Yale-Brown Obsessive Compulsive Scale and by the global response rate ("responder" equaling "much improved"). Eleven of 21 patients were responders with fluvoxamine compared with 2 of 19 patients with desipramine. Fluvoxamine, but not desipramine, was also effective in reducing the severity of "secondary" depression. Fluvoxamine-induced improvement in symptoms of obsessive-compulsive disorder was not correlated with the severity of baseline depressive symptoms. This study provides additional evidence that the acute serotonin reuptake properties of a drug are predictive of its anti-obsessive-compulsive efficacy. It is hypothesized that the mechanism of action of serotonin reuptake inhibitors in obsessive-compulsive disorder may be related to chronic treatment-induced adaptive changes in presynaptic serotonin receptor function (eg, autoreceptor desensitization) and/or indirect influences on dopaminergic function (eg, in the basal ganglia).
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PMID:Specificity of serotonin reuptake inhibitors in the treatment of obsessive-compulsive disorder. Comparison of fluvoxamine and desipramine. 202 4


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