Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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The efficacy and tolerability of the selective 5-HT reuptake inhibitor fluvoxamine were compared with the tricyclic dothiepin in 52 elderly (age greater than 64 years) hospital patients in a multi-centre double-blind randomised trial. Patients met DSM-III criteria for 'major depressive episode' and scored greater than 29 on the Montgomery Asberg Depression Rating Scale (MADRS) after a one-week placebo baseline. Active treatment was for six weeks. The dosage of both drugs was 50 mg nocte for three days, 100 mg nocte for the remainder of the first week, thereafter increasing to a maximum of 200 mg/day according to response/tolerance. MADRS scores improved by 63.5% with fluvoxamine and 60.0% with dothiepin; there were no significant differences between treatments at any assessment. Nausea, dizziness, headache, somnolence and constipation in both groups, plus dry mouth and asthenia in the dothiepin group were more frequent than single reports. Two patients in each group discontinued treatment owing to unwanted effects. There were no clinically significant changes in haematological, biochemical or cardiovascular parameters.
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PMID:A double-blind, randomised comparison of fluvoxamine with dothiepin in the treatment of depression in elderly patients. 181 Mar 58

Buspirone (Buspar) is a azaspirodecanedione anxiolytic agent. Its mechanism of action is extremely complex, but current investigations indicate that its main neuropharmacologic effects are mediated by the 5-HT1A receptors. Other neuroreceptor systems could be involved, as buspirone displays some affinity for DA2 autoreceptors and 5-HT2 receptors. It has been proposed that inhibition of synthesis and release of serotonin result through the combined interactions of neuroreceptors and secondary messenger systems. This action leads to inhibition of the firing rate of 5-HT-containing neurons in the dorsal raphe. From this novel profile, that differs from that of the benzodiazepines, buspirone lacks anticonvulsant and muscle-relaxant properties, and causes only minimal sedation. The drug is rapidly absorbed after oral administration, with a mean bioavailability of 3.9%. After a single oral dose, the mean elimination half-life is 2.1 hours. Buspirone is mainly bound to albumin and alpha 1-acid glycoprotein. It is metabolized to an active metabolite 1-(2-pyrimidinyl) piperazine (1-PP). The mean elimination half-life of 1-PP is 6.1 hours. Buspirone is indicated in the treatment of generalized anxiety disorders. Its efficacy is comparable to the benzodiazepines. Its use in depression and panic disorders requires further investigation. When combined with alcohol or given alone, psychomotor impairment was not detected. Abuse, dependence, and withdrawal symptoms have not been reported. The frequency of adverse effects is low, and the most common effects are headaches, dizziness, nervousness, and lightheadness. Buspirone should be added to drug formularies and could represent a significant addition in psychopharmacology.
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PMID:Buspirone: an update on a unique anxiolytic agent. 304 84

In both acute and long term clinical studies, the antihypertensive effects of the S2-serotonergic receptor antagonist ketanserin are more marked in the elderly than in younger patients. The acute effect of ketanserin 10mg intravenously was studied in 57 patients between 25 and 90 years and a significant negative correlation was shown between age and the decrease in both systolic and diastolic blood pressure. In longer term studies ketanserin has been compared with metoprolol and hydrochlorothiazide in patients below and above 60 years. Both ketanserin and the diuretic showed greater antihypertensive efficacy in the elderly, whereas the beta-blocker did not. Data from 15 double-blind studies from the ketanserin International Data File confirm the relationship between age and antihypertensive efficacy. With respect to adverse effects of ketanserin, dizziness, somnolence and dryness of the mouth were commoner in younger than older patients. These effects were not the result of smaller dose requirements in the elderly, and there was no obvious pharmacokinetic reason (e.g. alteration in drug clearance) for the difference. Two theoretical possibilities for the differential age effect of ketanserin are advanced. First the smaller effect in the young may be due to activation of homeostatic mechanisms limiting its antihypertensive activity, or second, some selective (undefined) effect operative in the elderly may be responsible. It is known from animal studies that serotonin shows increased vasoconstrictor properties in the presence of extensive atheroma. Antagonism of this effect may account for the greater vasodilator and antihypertensive effect of ketanserin in elderly patients. This, however, is speculative and does not take into account the complex antihypertensive action of ketanserin. The role of serotonin in cardiovascular control is complex. Its effects depend on the species studied, the vascular bed being investigated, the dose used and the experimental conditions employed. Serotonin has central cardiac and peripheral vascular actions relevant to cardiovascular control. In the peripheral vasculature it can produce vasodilatation or vasoconstriction by either direct or indirect mechanisms. If this complexity were not confusing enough, the nomenclature of the receptors on which serotonin acts is under intense current debate, and little uniformity exists as to the terminology to be used. The terms of this review will be very specific.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ageing, serotonin and ketanserin. 307 62

Aggregating platelets release serotonin, which induces contraction of most vascular smooth muscle by activation of S2-serotoninergic receptors. Serotonin released in the circulation may contribute to the increase in peripheral resistance of hypertension as the responsiveness of blood vessels from hypertensive animals and humans to the vasoconstrictor action of the monoamine is augmented. The data obtained with the new antihypertensive agent ketanserin may favor that interpretation. Ketanserin is a selective S2-serotoninergic antagonist with additional alpha 1-adrenergic blocking properties. In humans, it has a terminal half-life of 12 to 25 hours and is eliminated predominantly by the liver. The hemodynamic profile of ketanserin is that of a vasodilator drug with actions on both resistance and capacitance vessels. On short-term intravenous administration, it lowers blood pressure in hypertensive patients with minimal reflex changes in cardiovascular function. When given orally long term to hypertensive patients, ketanserin causes a sustained reduction in arterial blood pressure, comparable to that obtained with either beta-adrenergic blockers or diuretics. Several studies have shown a greater efficacy in older (greater than 60 years of age) than in younger patients independent of starting pressure. Side effects mainly consist of dizziness, somnolence, and dry mouth, but they are usually not severe. The mechanism underlying the antihypertensive effect of ketanserin is unclear. It cannot be attributed to either S2-serotoninergic or alpha 1-adrenergic blockade alone, but an interaction between the two effects appears to be required.
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PMID:Serotoninergic mechanisms in hypertension. Focus on the effects of ketanserin. 327 10

In an open, clinical trial comprising a total of 49 depressed in-patients, a new selective 5-HT uptake inhibitor citalopram was administered by intravenous infusion in doses of 20-60 mg once daily for per 3 weeks. The therapeutic effect was assessed globally and by means of the CPRS subscale for depression (MADRS). About 40 per cent of the patients showed a complete response whereas about 25 per cent showed a partial response. Side effects which were rated globally and recorded according to a check-list were generally mild and infrequent. The side-effects most frequently observed were tremor, drowsiness, and dizziness which occurred in about 15 per cent of the patients.' Three patients were withdrawn prematurely because of nausea and one because of a skin rash. Cardiovascular recordings were normal except for one patient, who developed a hypertension which may have been related to the test drug. No pathological laboratory values were detected during the trial period. The authors conclude that intravenously administered citalopram is well suited for the treatment of depressed patients.
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PMID:[Citalopram. An open study of a highly selective serotonin-uptake inhibitor administered by infusion to depressive patients]. 331 9

Citalopram, a selective 5-HT uptake inhibitor with antidepressant properties, was assessed in three studies in 12 healthy subjects using a battery of EEG, psychological, subjective and symptomatic measures. Study A involved the administration of citalopram, 20 mg and 40 mg, amitriptyline 50 mg and placebo in single dose using a balanced cross-over design. The test battery was applied before, and 1 and 3 h after each drug. Citalopram decreased slow-wave EEG activity whereas amitriptyline increased power in most EEG wavebands. Citalopram increased tapping rate and symbol copying whereas amitriptyline impaired these and other psychomotor tasks. Subjectively, amitriptyline was much more sedative than citalopram and produced more complaints of dry mouth. Study B comprised the administration of citalopram in the usual clinical dose of 40 mg, amitriptyline in the low clinical dose of 75 mg and placebo, each given for 9 nights using a balanced cross-over design. The test battery was applied on the first morning (pre-drug) and on the morning after the last nightly dose. None of the physiological tests showed any drug effects. Subjectively, citalopram was associated with feelings of shaking, nausea, loss of appetite and physical tiredness; amitriptyline produced feelings of shaking, nausea, loss of appetite, dryness of mouth, irritability, dizziness and indigestion; in general, amitriptyline effects were more marked than those of citalopram. Plasma samples were taken on the last day and plasma concentrations of both drugs and their metabolites were found to be in the expected range for the regimens used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of citalopram in single and repeated doses and with alcohol on physiological and psychological measures in healthy subjects. 346 75

Dialysis-induced hypovolemia in renal patients might accompany with decreased sympathetic tone and decreased baroreflex sensitivity. Present study was undertaken to elucidate the sympathetic nervous activity in terms of biogenic amines [plasma norepinephrine (NE), epinephrine (E) concentrations, dopamine-beta-hydroxylase activity (DBH) and plasma serotonin (5-HT) concentration] in 17 patients with chronic renal failure in whom renal hemodialysis were continuously performed. During pre-dialysis period, in these hemodialysis patients, heart rate, systolic blood pressure and plasma 5-HT were significantly elevated as compared with those on sex and age-matched controls; plasma NE and plasma DBH were not changed in these hemodialysis patients as compared with those in controls. After hemodialysis, increased plasma NE and increased DBH were observed in parallel with the significant weight loss. Mean blood pressure did not change after dialysis. Dialysis produced an increasing tendency of heart rate. Dialysis also produced a significant decrease in plasma 5-HT. Hemodialysis-induced weight loss was approximately 2 kg body weight after 5 hours dialysis; these patients were done 3 times dialysis during one week. However, hypotension and dizziness were not demonstrated under this condition. Present study revealed that long term maintenance hemodialysis produced increased sympathetic nervous system activity; the assumed explanation would be relevant to the simultaneous recovery of baroreflex sensitivity and sympathetic tone, because of the long-term continuous hemodialysis.
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PMID:[The function of the sympathetic nervous system determined by humoral factors in the maintenance hemodialysis patients]. 372 95

The aim of this study was to evaluate the safety of zimeldine, a 5-HT reuptake inhibitor, in the long-term treatment of depressive disorders. The study was an open label, multicentre investigation involving 147 patients who were suffering from depressive illness and who needed long-term anti-depressant treatment. Sixty-five patients completed the intended treatment period of 1 year, 75 terminated prematurely, and 7 are still in the programme. The reasons for termination were mainly ineffectiveness of the drug and adverse reactions. During the long-term treatment the most common emergent symptoms were, in order of decreasing frequency, dizziness, dry mouth, sleep disorders, sweating, tremor, nausea and headache. The side-effects were, however, mild and they generally decreased during the treatment period. No new adverse symptoms were reported. In the long-term treatment group, body weight showed a slight mean decrease. Clinical chemistry and cardiovascular investigations were judged to show no changes of clinical importance. It is concluded that zimeldine was shown to be a safe drug in this 1-year treatment programme of depression.
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PMID:The safety of zimeldine in long-term use in depressive illness. 623 Aug 89

Drug development in psychiatry has evolved from a process dependent on chance discovery to one based on rationally targeting specific mechanisms of action believed to be important in the pathophysiology underlying psychiatric syndromes. Antidepressant pharmacotherapy is the first area to have substantially benefited from this evolution. Serotonin selective reuptake inhibitors (SSRIs) were the first class of psychiatric medications developed based on such molecular targeting. Nefazodone is a new antidepressant that combines blockade of the serotonin-2 receptor with serotonin uptake inhibition. Perhaps as a result of this dual action, nefazodone caused fewer complaints of nervousness (e.g., agitation, anxiety), insomnia, and tremors and a higher incidence of confusion, dizziness, and vision disturbance than do other advanced generation antidepressants based on several different ways of assessing the relative incidence of these adverse effects. Reports of sexual dysfunction on nefazodone and bupropion treatment were lower than on treatment with other recently released antidepressants.
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PMID:Comparison of the tolerability of bupropion, fluoxetine, imipramine, nefazodone, paroxetine, sertraline, and venlafaxine. 764 68

Tianeptine is a novel antidepressant agent, both structurally (modified tricyclic) and in terms of its pharmacodynamic profile. Unlike other antidepressant agents, tianeptine stimulates the uptake of serotonin (5-hydroxytryptamine; 5-HT) in rat brain synaptosomes and rat and human platelets, increases 5-hydroxyindoleacetic acid (5-HIAA) levels in cerebral tissue and plasma, and reduces serotonergic-induced behaviour. Tianeptine reduces the hypothalamic-pituitary-adrenal response to stress, antagonises stress-induced behavioural deficits and prevents changes in cerebral morphology. The antidepressant efficacy of tianeptine, as shown in 2 trials of patients with major depression or depressed bipolar disorder with or without melancholia, is greater than that of placebo. In patients with major depression without melancholia or psychotic features, depressed bipolar disorder or dysthymic disorder, the antidepressant efficacy of short term (4 weeks to 3 months) tianeptine therapy appears to be similar to that of amitriptyline, imipramine and fluoxetine and may be superior to that of maprotiline in patients with coexisting depression and anxiety. However, submaximal dosages of amitriptyline and maprotiline were used in these studies. Preliminary evidence suggests that tianeptine may also be effective in patients with endogenous depression. Progressive therapeutic improvements have been observed with up to 1 year of tianeptine treatment, and long term therapy may reduce the rate of relapse or recurrence. Tianeptine is effective in the treatment of depression in elderly and post-alcohol-withdrawal patient subgroups. Tianeptine was more effective in reducing psychic anxiety than placebo in patients with major depression or depressed bipolar disorder with or without melancholia. The overall anxiolytic properties of tianeptine in patients with coexisting depression and anxiety appear to be similar to those of amitriptyline, imipramine and fluoxetine and may be superior to those of maprotiline, although submaximal dosages of amitriptyline and maprotiline were used. Studies of tianeptine in patients with primary anxiety have not been conducted. Tianeptine is well tolerated in the short (3 months) and long (up to 1 year) term. The incidence of dry mouth (38 vs 20%), constipation (19 vs 15%), dizziness/syncope (23 vs 13%), drowsiness (17 vs 10%) and postural hypotension (8 vs 3%) are greater with amitriptyline than with tianeptine. Insomnia and nightmares occur in more tianeptine than amitriptyline recipients (20 vs 7%). The relative lack of sedative, anticholinergic and cardiovascular adverse effects with tianeptine makes it particularly suitable for use in the elderly and in patients following alcohol withdrawal; these patients are known to have increased sensitivity to the adverse effects associated with psychotropic drugs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tianeptine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depression and coexisting anxiety and depression. 777 14


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