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)

Vasodilator responses to dopexamine, fenoldopam and dopamine, which are known to have agonist activity at D1-dopamine receptors, were examined in the rat isolated perfused kidney preparation. Perfusion pressure was raised by perfusing with the thromboxane TxA2 analogue, U46619, and vasodilator responses were observed as dose-related falls in perfusion pressure. Propranolol (10(-6) M) and prazosin (10(-6) M) were present throughout to eliminate beta 2 and alpha 1-adrenoceptor-mediated responses, respectively. The vasodilator responses were antagonized by SCH23390 (10(-9) M), indicating that they were mediated via D1-receptors. The displacements of the dose-response curves for fenoldopam, dopexamine and dopamine were, however, non-parallel with significant depression of the maxima to 30.2, 37.9 and 34.3%, respectively. In the presence of SCH23390 (10(-8) M) and prazosin (10(-6) M), dopexamine, isoprenaline and noradrenaline produced dose-related renal vasodilation. This was antagonized by propranolol indicating a role for beta-adrenoceptors. In the case of dopexamine, the maximum response was depressed in the presence of propranolol. The reason for the atypical blockade of vasodilator responses by SCH23390 was investigated. One possibility was the appearance of transient vasoconstrictor responses at higher doses of fenoldopam, dopexamine and dopamine, usually preceding the vasodilatation. The possibility was therefore considered that the vasoconstriction may have opposed the usual vasodilation at high doses and thus limited the size of the maximum vasodilation in the presence of SCH23390. The vasoconstriction by fenoldopam was not antagonized by S-sulpiride, the D2-receptor antagonist but was blocked by mianserin and therefore attributed to 5-HT2 receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Atypical antagonism of D1-receptor-mediated vasodilator response in the perfused kidney by SCH23390. 747 26

The 5-HT3 receptor blocking properties of YM060, YM114 (KAE-393), granisetron and ondansetron were examined in the vagus nerve and cerebral cortex of rats. 5-HT and 2-methyl-5-HT induced dose-dependent depolarizations of rat isolated vagus nerve with EC50 values of 2.53 (1.93-3.33) x 10(-6) and 4.03 (2.87-5.66) x 10(-6) M, respectively. YM060, YM114 and granisetron dose-dependently antagonized the depolarization of the rat vagus nerve induced by 5-HT, with decreases in the slope and maximal response at higher concentrations. Apparent pA2 values for these antagonists were 10.27 +/- 0.09, 10.12 +/- 0.16 and 9.44 +/- 0.40, respectively. Ondansetron produced a clear rightward shift of the concentration-response curve to 5-HT. The pA2 value was 8.63 (8.23-9.68). YM060 and YM114 at up to 10(-5) M produced no significant depression of the depolarizing responses to DMPP and GABA. YM060, YM114, granisetron and ondansetron displaced specific binding of [3H]GR65630 to rat cortical membranes with pKi values of 10.48 (10.41-10.57), 10.24 (10.18-10.28), 9.15 (9.02-9.28) and 8.70 (8.64-8.77), respectively. An excellent correlation (r = 0.97) was obtained between pA2 values in the vagus nerve and pKi values in the cerebral cortex. YM060, YM114, granisetron and ondansetron showed low affinities for 5-HT1A, 5-HT2 receptor, adrenergic alpha 1, alpha 2, dopamine D2, muscarinic M2, mu-opioid, benzodiazepine and histamine H1 receptors. These results support the possibility that the same type of 5-HT3 receptor occurs in rat vagus nerve and cerebral cortex.
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PMID:Comparative study of the affinities of the 5-HT3 receptor antagonists, YM060, YM114 (KAE-393), granisetron and ondansetron in rat vagus nerve and cerebral cortex. 756 99

To determine whether there are characteristics distinguishing placebo responders from nonresponders, we studied 37 outpatients meeting DSM-III-R criteria for depression who were enrolled in controlled drug trials and 14 control subjects. Clinical data and blood samples were collected on admission and after a 7- to 10-day placebo washout. All patients experiencing a 40% drop in the Hamilton Rating Scale for Depression (HRSD) at the time of the second evaluation were considered placebo responders. There were no statistically significant differences between the two groups in clinical variables. Platelet markers distinguished the groups: Most notably, placebo nonresponders had the lowest 5-HT uptake site density values, placebo responders had intermediate values, and normal controls had the highest values. Placebo responders and placebo nonresponders had higher 5-HT uptake affinity values. No significant differences were observed among the groups in platelet 5-HT2 receptor site density or affinity values. These results suggest that platelet serotonin characteristics, but not common clinical characteristics, may distinguish depressed patients who do and do not respond to placebo.
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PMID:Platelet binding characteristics distinguish placebo responders from nonresponders in depression. 757 8

In the learned helplessness procedure, rats can be differentiated into two distinct groups. Learned helplessness (LH) rats do not learn to escape a controllable shock while non-learned helplessness (NLH) rats learn this response. This deficit in performance in LH rats lasted for 11 days. In LH rats, pretreatment with acute desipramine (15 mg/kg i.p.) or chronic diazepam (0.95 mg/kg/day p.o. for 7 days) did not produce recovery from this deficit of performance, but pretreatment with chronic desipramine (17.7 mg/kg/day p.o. for 7 days) or chronic mianserin (6.1 mg/kg/day p.o. for 7 days) led to recovery. Before presentation of uncontrollable shock, there was no difference between LH and NLH rats, but 11 days after the shock, head shakes induced by (+/-)-1-(2,5-demethoxy-4-iodophenyl)-2-aminopropane (DOI) in LH rats was significantly more frequent than those in NLH and naive rats without change of [3H]ketanserin binding. The basal corticosterone level was higher in LH rats than in NLH rats. These findings suggest that the learned helplessness model is a reliable animal model of depression accompanied by 5-HT2 receptor hypersensitivity.
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PMID:Increased 5-HT2 receptor-mediated behavior 11 days after shock in learned helplessness rats. 758 99

Although many serotonin (5-hydroxytryptamine; 5-HT) receptors have been identified, our knowledge of many of the subtypes is limited. However, we do know that 5-HT1A agonists are involved in the treatment of certain anxiety disorders, that 5-HT1C and 5-HT2 receptor antagonists may be indicated for the treatment of generalized anxiety disorder, and that 5-HT1D receptor agonists are used in the treatment of migraine. Recent research has identified that various abnormalities in serotonergic function are involved in the pathogenesis of depression and anxiety, and has facilitated the development of new pharmacological agents with great therapeutic potential, for example the selective serotonin reuptake inhibitors (SSRIs). These agents appear to be effective in the treatment of many anxiety states and may have greater efficacy than other agents in the treatment of certain affective disorders. As the central serotonergic system continues to be "mapped", newer and more selective drugs are likely to be introduced, thereby possibly improving the overall successful management of depression and anxiety disorders.
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PMID:The role of serotonin in depression and anxiety. 762 23

Serotonergic neurotransmission represents a complex mechanism involving pre- and post-synaptic events and distinct 5-HT receptor subtypes. Serotonin (5-HT) receptors have been classified into several categories, and they are termed as 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6 and 5-HT7 type receptors. 5-HT1 receptors have been further subdivided into 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E and 5-HT1F. 5-HT2 receptors have been divided into 5-HT2A, 5-HT2B and 5-HT2C receptors. All 5-HT2 receptor subtypes are linked to the multifunctional phosphoinositide (PI) signalling system. 5-HT3 receptors are considered ion-gated receptors and are also linked to the PI signalling system by an unknown mechanism. The 5-HT2A receptor subtype is the most widely studied of the 5-HT receptors in psychiatric disorders (for example, suicide, depression and schizophrenia) as well as in relation to the mechanism of action of antidepressant drugs. The roles of 5-HT2C and 5-HT3 receptors in psychiatric disorders are less clear. These 5-HT receptors also play an important role in alcoholism. It has been shown that 5-HT2A, 5-HT2C and 5-HT3 antagonists cause attenuation of alcohol intake in animals and humans. However, the exact mechanisms are unknown. The recent cloning of the cDNAs for 5-HT2A, 5-HT2C and 5-HT3 receptors provides the opportunity to explore the molecular mechanisms responsible for the alterations in these receptors during illness as well as pharmacotherapy. This review article will focus on the current research into the pharmacological properties, molecular biology, and clinical correlates of 5-HT2A, 5-HT2C and 5-HT3 receptors.
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PMID:Phosphoinositide system-linked serotonin receptor subtypes and their pharmacological properties and clinical correlates. 778 83

Dysfunction of brain serotonergic symptoms may be a factor in the mood and behavioral disturbances associated with depression. Platelet serotonin measures represent indirect but easily obtainable indices of brain serotonin function. To examine the specificity of relationships between cognitive and vegetative symptom groupings and platelet serotonin measures, we assessed 35 depressed outpatients using the Hamilton Rating Scale for Depression and collected platelets after a minimum 3-week drug-free period. Platelets were also collected from 14 controls. The results showed that depressed patients had lower platelet serotonin (5-HT) uptake site density values than controls and that 5-HT uptake site density values were inversely correlated with the severity of cognitive symptoms of depression. Platelet 5-HT2 receptor density values were higher in depressed patients than controls, and there was a trend toward a direct correlation between the cognitive symptoms of depression and 5-HT2 receptor density values. Neither platelet measure showed any relationship with the severity of the vegetative symptoms of depression.
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PMID:Platelet serotonin markers and depressive symptomatology. 778 57

This study deals with the characterization of 5-hydroxytryptamine (5-HT, serotonin) receptors positively linked to adenylyl cyclase in membranes from pig brain caudate. 5-HT and related agonists induced a concentration-dependent stimulation of adenylyl cyclase activity in pig caudate membranes, with the following rank order of potency (mean pEC50 values): 5-HT (7.1) > or = 5-methoxytryptamine (6.9) > 5-carboxamidotryptamine (5.6) > sumatriptan (< 5). Maximal stimulation by 5-HT averaged 35 pmol cyclic AMP/min/mg protein over a basal activity of 159 pmol cyclic AMP/min/mg protein. 5-Methoxytryptamine and 5-carboxamidotryptamine had similar efficacies to that of 5-HT, whereas sumatriptan was about half efficacious. Other compounds known as agonists at some 5-HT receptors were weakly potent (mean pEC50 values < 5). They include the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin hydrobromide (8-OH-DPAT), the 5-HT4 receptor agonist, renzapride and the 5-HT2 receptor agonist, (1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane) (DOI). In antagonist studies, methiothepin (0.1 and 1 mumol/l) shifted the 5-HT curve to the right with no depression of the Emax, yielding pKB values of 7.4-8.0. Clozapine (1 mumol/l) also produced surmountable antagonism of 5-HT-induced effects (pKB 6.9). Ketanserin (10 mumol/l) weakly antagonized 5-HT (pKB 5.0). The 5-HT4 receptor antagonists, tropisetron (ICS 205-930) and SDZ 205-557 (2-methoxy-4-amino-5-chloro-benzoic acid 2-(diethylamino) ethyl ester), each at 1 mumol/l, did not significantly alter the concentration-response curve of 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:5-Hydroxytryptamine receptors with a 5-HT6 receptor-like profile stimulating adenylyl cyclase activity in pig caudate membranes. 784 73

Serotonin(5-HT)-stimulated intracellular calcium(Ca) mobilization was measured in the platelets of depressed patients to assess 5-HT2 receptor function. The 5-HT-induced Ca response was significantly higher in unmedicated patients with bipolar depression and melancholic major depression than in those with non-melancholic major depression and normal controls. The enhanced Ca response to 5-HT failed to correlate with severity of depressive symptoms. In patients with bipolar disorder and melancholic major depression, there was no significant difference in 5-HT-stimulated Ca response between the unmedicated group and those in remission. These results suggest that 5-HT2 receptor function is increased in some types of depression, and raise the possibility that the enhanced Ca response to 5-HT may be trait dependent rather than state dependent.
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PMID:Serotonin-induced platelet intracellular calcium mobilization in depressed patients. 786 40

The ability of SR 46349B [trans,4-([3Z)3-(2-dimethylaminoethyl)oxyimino- 3(2-flurophenyl)propen-1-yl]phenol hemifumarate], a 5-HT2 receptor antagonist, to block the changes in respiratory activity induced by serotonin was analysed by using brain stem-spinal cord preparations from newborn rats. The increases in respiratory frequency elicited by serotonin (and 5-HT1A receptor agonist) were not suppressed by SR 46349B. The tonic discharge of cervical motoneurons and the depression of inspiratory hypoglossal activity elicited by serotonin (and 5-HT2 receptor agonist) were reduced in a dose-dependent manner by SR 46349B. These results confirm that activation of 5-HT1A and 5-HT2 receptors influences respiratory frequency and motoneuronal output, respectively.
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PMID:Further evidence that various 5-HT receptor subtypes modulate central respiratory activity: in vitro studies with SR 46349B. 795 97


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