Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P08908 (5-HT1A)
 5,574 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Antihypertensive effects resulting from alpha 1-adrenoceptor blockade and stimulation of central nervous 5-HT1A receptors were compared with the effects arising from stimulation of 5-HT1A receptors alone during arterial hypertension. 2. Urapidil and 5-methyl-urapidil were less effective in decreasing arterial blood pressure than the lowest dose of the selective 5-HT1A receptor agonist, flesinoxan. After the higher dose of urapidil, a certain dampening of barareceptor reflex was found which was also seen with flesinoxan. 3. Flesinoxan was the only drug which did not reduce the exercise-induced increase in systolic arterial blood pressure. 4. Stimulation of 5-HT1A receptors alone, which is assumed to occur with flesinoxan, exerted antihypertensive activity only at low doses, without inducing reflex tachycardia at rest. 5. Only the combined effects of alpha 1-adrenoceptor blockade and 5-HT1A receptor stimulation, as assumed to occur with urapidil and 5-methyl-urapidil, lead to both a decrease in arterial blood pressure at rest and during exercise.
 ...
PMID:Influence of alpha 1-adrenoceptor blockade and/or 5-HT1A agonism on blood pressure and heart rate at rest and during exercise in hypertensive dogs. 135 78

Pretreatment (15 min) of male rats with gepirone given parenterally (10 mg/kg i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 micrograms) blocks the rapidly reversible increase in brain tryptophan hydroxylase activity and 5-hydroxyindolamine acetic acid tissue levels seen in vitro after 1-h acute sound stress. Chronic gepirone treatment over 28 days (40 mg/day s.c.) prevents the stable enzyme activity increase induced by repeated sessions of sound stress, and the rapidly reversible increase always observed following sound stress. The gepirone metabolite, 1-(2-pyrimidinyl)-1-piperazine, is inactive in each of these experiments. Transient blood pressure elevations occur with each sound presentation, but no persistent hypertension is observed with repeated sound-stress exposures. Gepirone may block the sound stress-induced biochemical increases by its inhibition of serotonergic neuronal firing in the dorsal raphe nucleus that is mediated by its agonist action at the somatodendritic (5-HT1A) autoreceptors.
 ...
PMID:Effect of gepirone on increases in tryptophan hydroxylase in response to sound stress. 137 31

The effects of serotonin (5-hydroxytryptamine; 5-HT) on the cardiovascular system are complex. These effects, consisting of bradycardia or tachycardia, hypotension or hypertension, and vasodilation or vasoconstriction are mediated by three main sets of receptors called 5-HT1-like, 5-HT2, and 5-HT3. In addition, recent findings suggest the participation of a putative 5-HT4 receptor. Though selective 5-HT1A receptor agonists can lower heart rate (and arterial blood pressure), 5-HT usually lowers heart rate by eliciting an initial short-lasting hypotension due to bradycardia (von Bezold-Jarisch-like reflex) via 5-HT3 receptors located on sensory vagal nerve endings in the heart. Once this bradycardia reflex is suppressed--for example, during deep anesthesia, vagotomy, or spinal section--5-HT can increase heart rate in different species by a variety of mechanisms. Myocardial 5-HT1-like, 5-HT2, and 5-HT4 receptors appear to be involved in the cat, rat, and pig, respectively. 5-HT-induced tachycardia in the dog and rabbit is due mainly to release of catecholamines and involves 5-HT2 receptors on the adrenal medulla and 5-HT3 receptors on postganglionic cardiac sympathetic nerve fibers. Recently, 5-HT3 receptors also have been implicated in the 5-HT-induced tachycardia in the conscious dog. The blood pressure response to 5-HT is usually triphasic and consists of a von Bezold-Jarisch-like reflex, a middle pressor phase, and a longer-lasting hypotension. The pressor response is a consequence of vasoconstriction mediated via 5-HT2 receptors; however, vasoconstriction in the dog saphenous vein and cephalic arteries and arteriovenous anastomoses is due to stimulation of 5-HT1-like receptors. The depressor response exclusively involves 5-HT1-like receptors located at four different sites: (a) central nervous system (decrease in sympathetic and increase in vagal nervous activity), (b) sympathetic nerve terminals (reduction of transmitter release), (c) vascular smooth muscle (vasodilatation), and (d) vascular endothelium (release of a relaxant factor, probably nitric oxide). Arteriolar dilatation, together with the constriction of arteriovenous anastomoses, leads to an increase in nutrient (tissue; capillary) blood flow. The 5-HT1-like receptors are heterogeneous in nature; however, apart from the resemblance of the central nervous system 5-HT1-like receptor causing hypotension and bradycardia to the 5-HT1A binding subtype, the relationship of the other 5-HT1-like receptors to 5-HT1 binding subtypes is still debatable.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Cardiovascular effects of serotonin agonists and antagonists. 170 84

Both intravenous and central administration of ketanserin, a 5-HT2 receptor antagonist, decrease blood pressure and sympathetic nerve activity, suggesting a central origin of its effects. However, ketanserin also possesses alpha 1-adrenoceptor blocking properties. Selective 5-HT2 receptor antagonists devoid of alpha 1-adrenoceptor blocking properties, e.g. LY 53857 and cinanserin, fail to reduce blood pressure and sympathetic nerve activity. In addition, 5-HT2 receptor agonists increase blood pressure and sympathetic nerve discharge. Therefore, it seems improbable that blockade of central 5-HT2 receptors alone could lead to a reduction in blood pressure. In contrast, the selective 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan decrease blood pressure and heart rate by a centrally-mediated decrease in sympathetic tone and an increase in vagal tone. The sympatho-inhibitory effects of 5-HT1A receptor agonists result from the stimulation of postsynaptic 5-HT1A receptors within the ventrolateral pressor area. These results suggest that selective 5-HT1A receptor agonists acting in the central nervous system could be developed for the treatment of hypertension. Indeed, drugs such as flesinoxan and urapidil are effective in this setting.
 ...
PMID:Central 5-hydroxytryptamine (5-HT) receptors in blood pressure regulation. 181 50

The 5-HT1A-receptor antagonist (S)-UH-301 (S)-5-fluoro-8-hydroxy-2- (dipropylamino)tetralin) completely antagonized the hypotension and bradycardia induced by (R) = 8-OH DPAT [R)-8-hydroxy-2- (dipropylamino)tetralin) in conscious rats. (S)-UH-301 alone induced a weak hypertension, which might be due to its 5-HT1A-receptor antagonistic properties. (R)-UH-301 induced effects similar to those of (R)-8-OH DPAT, i.e., a short initial phase of hypertension followed by a long-lasting hypotension and bradycardia. Thus, (R)-UH-301 behaves as a 5-HT1A-receptor agonist and (S)-UH-301 as a 5-HT1A-receptor antagonist, abolishing the effects induced by (R)-8-OH DPAT.
 ...
PMID:(S)-UH-301 antagonizes (R)-8-OH-DPAT-induced cardiovascular effects in the rat. 183 12

Serotonin (5-HT) is a potent bioactive substance known to function through a number of different receptor types and subtypes. In our attempt to develop new agents that would interact selectively at certain 5-HT receptors, especially the 5-HT1A subtype, 8-hydroxy-2-di-n-propylamino tetralin (8-OH-DPAT) served as a template for the design of novel agents sharing aspects of the pharmacophore of 8-OH-DPAT and 5-HT. 5-HT contains no center of asymmetry, and 8-OH-DPAT shows only very modest stereospecificity for 5-HT1A receptors. To develop agents having enhanced potency and selectivity for the 5-HT1A site, several ring systems offering enhanced conformational rigidity which approximate the oxygen to nitrogen interatomic distances of 8-OH-DPAT and (to a lesser extent) 5-HT were synthesized. Exemplary ring systems include the 8-alkoxy-hexahydroindeno[1,2-c]pyrrole, 5-alkoxy-hexahydro-1H-indeno-[2,1-c]pyridine, and 9-alkoxy-hexahydro-1H-benz[e]isoindole systems. These conformationally restricted molecules demonstrated moderate stereospecificity in their interaction with the 5-HT1A binding site, which was enhanced in compounds with larger nitrogen substituents. Appropriate choice of such derivatives led to highly potent compounds selective for 5-HT1A sites compared with their activity at other 5-HT and/or adrenergic receptors. The pharmacological profile of compounds which appear to act as agonists at 5-HT1A receptors in the central nervous system to lower blood pressure in animal models of hypertension is presented.
 ...
PMID:Molecular design of novel ligands for 5-HT1A receptors. 188 79

Serotonin is a monoamine and is widely distributed in the human organism. Serotonin is synthesized from the amino acid tryptophane and is broken down via mono-amino-oxydase enzymes to 5-hydroxy-indol-acetic acid and by acetylizing and methylizing to melantonin. In 1986, a consensus concerning the classification of the serotonergic receptors was established. Three main classes were determined, viz: 5-HT1, 5-HT2 and 5-HT3. 5-HT1 receptors were further subdivided into A, B, C and D-receptors and, of these, the 5-HT1A-receptor is involved in the centrally mediated blood pressure control via reduction in the pre- and postganglionic sympathetic activity. The 5-HT2 receptors are primarily involved in control of peripheral blood pressure where agonizing results in vascular contraction of the large arteries and veins and thrombocyte aggregation. The 5-HT1 receptors are also involved peripherally in connection with release of relaxing factors derived from endothelium. In vitro and in animal experiments, it has been demonstrated that serotonin is capable of inducing arrhythmia and myocardial dysfunction via 5-HT3 receptors. Several preparations with effects on both the central and peripheral serotonergic receptors are already marketed for treatment of hypertension and other conditions.
 ...
PMID:[Serotonin and cardiovascular control]. 221 14

Serotonin (5-hydroxytryptamine; also called 5-HT) modifies cardiovascular activity by central as well as peripheral sites of action. When 5-HT is injected within the central nervous system, depending upon the dose and site of administration, either a pressor or a depressor effect is observed. Recent findings suggest that this depressor effect may be mediated by central "5-HT1-like" receptors, since certain compounds that exhibit a high affinity for the 5-HT1A binding site can reduce blood pressure by a central action in both hypertensive and normotensive animals. Peripherally, 5-HT elicits vasodilatation (both directly and indirectly via presynaptic sympathoinhibition and release of vasodilator substances from endothelium) or vasoconstriction (with associated amplification of noradrenaline response) of mainly "large" conductance arteries mediated by, respectively, "5-HT1-like" and 5-HT2 receptors. Of the various antagonists at 5-HT receptors, it is only ketanserin that effectively lowers arterial blood pressure. However, since it is unlikely that the very low concentrations of 5-HT in plasma exert a significant influence on the maintenance of peripheral vascular resistance, the blockade of 5-HT2 receptors by ketanserin does not seem to explain the reduction of blood pressure in hypertension. Indeed, apart from the undoubtedly potent 5-HT2 receptor blockade, ketanserin also has alpha 1-adrenoceptor antagonist, central vasomotor depressant, and "direct" vasodilator properties, which can explain its antihypertensive action.
 ...
PMID:Serotonin agonists and antagonists in experimental hypertension. 244 59

The role of serotonin (5-HT) in blood pressure (BP) regulation was reviewed. Central and peripheral 5-HT receptors can be divided into three receptor subtypes: 5-HT1 (5-HT1A, 5-HT1B, 5-HT1C), 5-HT2 and 5-HT3 receptors. The selective agonists and antagonists of these receptor subtypes are useful for investigating the BP regulation by 5-HT. The central 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produced hypotension and decreases in sympathetic nerve activity (SNA). This suggests that central 5-HT may cause decreases in both BP and SNA via 5-HT1A receptors. Since the 5-HT2 receptor antagonist ketanserin, which has an antihypertensive effect, decreased SNA and the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) increased SNA, central 5-HT2 receptors may be connected with the 5-HT-induced increases in both BP and SNA. On the other hand, ketanserin's antihypertensive effects via its 5-HT2 receptor blocking action in the vascular system indicates that peripheral 5-HT may contribute to the initiation or the maintenance of elevated vascular resistance in several forms of hypertension including essential hypertension. However, ketanserin also possesses alpha 1-adrenoceptor blocking action, and its precise antihypertensive mechanism has not been established. Further study of the antihypertensive mechanism of ketanserin will help clarify the precise role of 5-HT in BP regulation.
 ...
PMID:[Serotonin and blood pressure regulation--antihypertensive mechanism of ketanserin]. 257 64

Identification of 5-HT receptor subtypes--5-HT1A, 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 (possibly A and B), 5-HT3 subtypes, and possibly 5-HT4--has encouraged the manufacture of 5-HT receptor inhibitors with greater subtype specificity. However, it appears that the receptors interact, and drugs initially thought to be specific may have multiple actions. For some conditions such as anxiety/depression, almost all receptors are implicated. Clinical studies provide clear evidence that manipulation of the 5-HT system has a role in treating depression, anxiety, obsessional illness, migraine, and eating disorders. Interactions between the various receptor subtypes make it difficult to identify specific clinical functions. The 5-HT1A receptors may be involved in aggression, anorexia, and hypotension. The 5-HT1B receptors may be involved in aggression, while the 5-HT1C receptors may play a role in central aversion systems and anxiety/depression. The role of the 5-HT1D receptors remains speculative; 5-HT2 receptors appear to be involved in depression, anxiety, appetite, sleep, vasoconstriction, and hypertension. Many drugs that are effective in treating migraine are potent 5-HT2 antagonists. 5-HT3 antagonists at high doses are effective in treating nausea and at low doses in treating anxiety. Treatment of aggression, suicidal behaviour, addiction behaviour, memory impairment, dementia, and schizophrenia with 5-HT inhibitors requires further testing.
 ...
PMID:Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? 269 41


1 2 3 Next >>