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

The present experiments served to compare the effects of the 3 5-HT1 agonists, 8-OH-DPAT, 5-MeODMT and TFMPP on the blood pressure and heart rate of normotensive anaesthetized rats. All the agonists induced, after i.v. injection, a decrease in blood pressure and heart rate. The hypotensive effects of 5-MeODMT and TFMPP were preceded by an increase, suppressed by both ketanserin and methysergide. The decrease in blood pressure induced by 5-MeODMT and 8-OH-DPAT was not antagonized by ketanserin, cocaine (and methysergide for 8-OH-DPAT) but was antagonized by methysergide (for 5-MeODMT) and spiroxatrine (for both). Bradycardia was not susceptible to ketanserin and cocaine (for 5-MeODMT) or to ketanserin and methysergide (for 8-OH-DPAT) but to methysergide and spiroxatrine (for 5-MeODMT) and cocaine and spiroxatrine (for 8-OH-DPAT). These results suggested that the hypotension and bradycardia induced by 5-MeODMT and 8-OH-DPAT are due to the stimulation of '5-HT1-like' receptors and probably to the 5-HT1A subtype; the 5-MeODMT-induced hypertension being ascribed to the stimulation of 5-HT2 receptors.
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PMID:Comparison of effects of some 5-HT1 agonists on blood pressure and heart rate of normotensive anaesthetized rats. 295 2

The seronin or 5-hydroxytryptamine (5-HT) is a biogenic amine involved in diverse physiologic and physiopathological processes in the cardiovascular system. 5-HT may lower the arterial blood pressure by an action on central 5-HT1A receptors, or may increase it by stimulation of 5-HT2 receptors located in vascular smooth muscle. It has been postulated that hypofunction of 5-HT1A receptors, or the exaggerated stimulation of 5-HT2 receptor may be associated with arterial hypertension and that agonists of the first type (indorenate or 8-OH-DPAT) or antagonists of the second type (ketanserin or pelanserin) allow the control of arterial hypertension. On the other land, ketanserin and pelanserin attenuated the hemodynamic manifestations in an experimental model of thromboembolism, suggesting that 5-HT is involved in such phenomenon. Finally, 5-HT could be related with the presence of angor pectoris during hypertension or atherosclerosis, diseases that are associated with a lesional of the vascular endothelium, a condition that favors the 5-HT induced vasoconstriction in coronary arteries.
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PMID:[Serotoninergic receptors and cardiovascular diseases]. 765 75

With method of the radio binding assay (RBA), it was observed that in the present work that in normotensive Wistar rats, the specific binding of [3H] 8-OH-DPAT at 2.4 nmol/L concentration was about the same in hippocampus (7.62 +/- 0.24 pmol/mg), hypothalamus (8.18 +/- 0.63 pmol/mg) and lower brain stem (9.11 +/- 0.78 pmol/mg); whereas, in spontaneously hypertensive rats (SHR), these regional specific bindings were 2(+)-3+ times higher. Scatchard analyses showed that the Bmax was also higher than that of normotensive Wistar rats in hippocampus and hypothalamus, whereas the KD in hypothalamus was lower. The differences between SHR and normotensive rats in the 5-HT1A receptor contents in various brain regions appear to be related to one of the linking events in the generation of hypertension.
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PMID:[The characterization of 5-HT1A receptor in the central nervous system of the spontaneously hypertensive rats]. 797 18

Feeding a vitamin B6-deficient diet to rats causes a moderate hypertension. The blood pressure responses to 5-HT1A receptor agonists were studied in conscious vitamin B6-deficient hypertensive rats. They were all effective in lowering blood pressure with the following rank order of potency: 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) > flesinoxan > 5-methylurapidil > urapidil. The putative 5-HT1A receptor antagonist spiroxatrine by itself, did not have any effect on the blood pressure at the doses used (0.01-1 mumol/kg). However, dose dependently, it antagonized the hypotensive effect of flesinoxan and urapidil. The alpha 1-adrenoreceptor antagonist prazosin, on prior treatment, did not change the hypotensive effect of either flesinoxan or urapidil. The alpha 2-adrenoreceptor agonist clonidine dose dependently (0.01-0.1 mumol/kg) reduced blood pressure. This effect of clonidine was unaffected by spiroxatrine, but was dose dependently antagonized by the alpha 2-adrenoreceptor antagonist yohimbine. Binding studies with [3H]8-OH-DPAT indicated that the affinity and Bmax of 5-HT1A receptors was increased in vitamin B6-deficient hypertensive rats. The results suggest that decreased synthesis of 5-HT in brain regions and the consequent alterations in 5-HT receptors in the vitamin B6-deficient rats may be the underlying cause of the hypertension seen in these animals.
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PMID:Hypotensive action of 5-HT receptor agonists in the vitamin B6-deficient hypertensive rat. 848 25

Experiments were designed to test the hypothesis that activation of forebrain 5-HT1A receptors elicits cardiovascular responses. The microinjection of R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin [(+)-8-OH-DPAT], a selective 5-HT1A receptor agonist, in the preoptic area of conscious rats increased blood pressure and heart rate at doses of 0.2-20 nmol; lower doses (0.002 and 0.02 nmol) were ineffective. The concomitant administration of methiothepin, a non-selective 5-HT receptor antagonist, into the preoptic area attenuated the responses. In addition, the tachycardia elicited by (+)-8-OH-DPAT was abolished by the peripheral beta-adrenoceptor antagonist sotalol, but not by atropine methyl nitrate. Finally, the tachycardia, but not the hypertension, was also produced by (+)-8-OH-DPAT in urethane-anesthetized rats. These results suggest that activation of 5-HT1A receptors in the preoptic area or an adjacent region of the forebrain produces: (1) an increase in heart rate consistent with sympathoadrenal activation; and (2) an increase in blood pressure which might be the result of sympathoexcitation or secondary to behavioral arousal.
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PMID:Cardiovascular effects produced by R-(+)-8-hydroxy-2-(di-n-propylamino) tetralin in the preoptic area of conscious rats. 896 Aug 83

This review aims to describe the pharmacological bases for using urapidil, a recently introduced hipotensor, and to survey the literature on its therapeutic possibilities. The anesthesiologist often sees hypertension during surgery and must apply hypotensive treatment to prevent complications. Urapidil works mainly by antagonizing postsynaptic alpha-1-adrenergic receptors and stimulating 5-HT1A receptors, a double mechanism that provides vasodilation with moderate decrease in blood pressure without reflex tachycardia. Adverse side effects are rare and clinically unimportant. Onset is rapid after intravenous administration and duration of action is short; dose can be easily adjusted based on response and patient requirements. While urapidil has been used successfully in a variety of diseases and surgical procedures, its pharmacological characteristics make it particularly useful in patients at high cardiovascular risk or undergoing neurosurgery, in which results are good. Although the oral form is not sold in Spain, it is used in other countries to treat chronic high blood pressure. Urapidil is a hypotensor with a wide range of indications (critical hypertension, prophylaxis for hypertensive peaks and treatment of hypertension during surgery) and few side effects.
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PMID:[Urapidil in anesthesiology: pharmacology and indications]. 964 68

The mechanisms for the vascular actions of vasodilatory beta-blockers remain undetermined. For some kinds of beta-blockers, the involvement of nitric oxide (NO) has been suggested. We studied the effects of vasodilatory beta-blockers on renal perfusion pressure (RPP) and NO release in the rat kidney. Infusion of bopindolol, celiprolol, and nebivolol caused a dose-dependent reduction in RPP and an increase in NO release (RPP: bopindolol 10(-6) mol/L, -23+/-2%; celiprolol 10(-4) mol/L, -27+/-2%; nebivolol 10(-5) mol/L, -35+/-3%; NO: bopindolol 10(-6) mol/L, +33+/-2; celiprolol 10(-4) mol/L, +41+/-2; nebivolol 10(-5) mol/L, +45+/-5 fmol. min-1. g kidney-1, mean+/-SEM). Metergoline (10(-6) mol/L), a 5-hydroxytryptamine (5-HT)1/2 antagonist, or NAN-190 (10(-6) mol/L), a 5-HT1A antagonist, almost completely abolished the vasorelaxation and NO release caused by bopindolol, celiprolol, and nebivolol. However, neither propranolol nor bisoprolol decreased RPP. Celiprolol and nebivolol caused vasodilation in the rat thoracic aorta, and it was markedly reduced by endothelial denudation, Nomega-nitro-L-arginine methyl ester (10(-4) mol/L), or NAN-190 (10(-6) mol/L). In deoxycorticosterone acetate-salt hypertensive rats, 4-week administration of celiprolol (50 mg. kg-1. d-1 IV) restored the responses regarding RPP and NO release to acetylcholine. These results suggest that several beta-blockers exert their vasodilatory action through the 5-HT1A receptor/NO pathway and that treatment with these beta-blockers may protect against endothelial injury in hypertension.
Hypertension 1999 Jan
PMID:Effects of vasodilatory beta-adrenoceptor antagonists on endothelium-derived nitric oxide release in rat kidney. 993 Nov 49

Maintained stress produces a constellation of neurochemical and hormonal changes that involve both the hypothalamic-pituitary-adrenal axis and a variety of brain regions. Long-term stress can produce psychological and physiologic consequences including anxiety, depression, hypertension, impaired immune system function, and an increased risk of cancer and coronary heart disease. Negative responses to perceived job-related stress usually occur when an individual has relatively little control over the means to meet high job demands. Among the approaches to reduce workplace stress, changing the coping strategies of challenged employees, particularly by increasing decision latitude, can significantly relieve both the psychological and physiologic consequences. Nevertheless, behavioral intervention is not invariably successful, and benzodiazepines are often prescribed to manage inadequately alleviated anxiety. Evidence that excessive serotonergic neurotransmission may underlie anxiety has prompted the use of compounds such as buspirone. This partial agonist of the 5-HT1A receptor has been demonstrated to be as effective as benzodiazepines in controlling generalized anxiety symptoms and to have a more favorable side-effect profile.
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PMID:Stress: an overview of the literature with emphasis on job-related strain and intervention. 1015 Feb 61

The serotonergic innervation of the locus coeruleus paetly derives from the dorsal raphe nucleus (DRN). Using the push-pull superfusion technique, we investigated whether and to what extent the release of serotonin and the extracellular concentration of its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the locus coeruleus are influenced by the neuronal activity of the DRN. In anaesthetized rats, a push-pull cannula was inserted into the locus coeruleus, which was continuously superfused with artificial cerebrospinal fluid (aCSF). Serotonin and 5-HIAA levels in the superfusate were determined by HPLC combined with electrochemical detection. Electrical stimulation (5 Hz, 300 microA, 1 ms) of the DRN for 5 min, or its chemical stimulation by microinjection of glutamate (3.5 nmol, 50 nl), led to an increased release of serotonin in the locus coeruleus and to a slight (2 mmHg) decrease in blood pressure. Superfusion of the locus coeruleus with tetrodotoxin (1 microM) abolished the increase in the release rate of serotonin evoked by electrical stimulation of the DRN, while the slight fall in blood pressure was not influenced. Thermic lesion (75 degrees C, 1 min) of the DRN elicited a pronounced decline in serotonin release rate within the locus coeruleus, the maximum decrease being 52%. The decrease in the release of serotonin was associated with a long-lasting rise in blood pressure. Microinjection of the serotonin neurotoxin 5,7-dihydroxytryptamine (5 microg, 250 nl) into the DRN led to an initial increase in the serotonin release rate that coincided with a short-lasting fall in blood pressure. Subsequently, the release of serotonin was permanently reduced and was associated with hypertension. Microinjection of the 5-HT1A receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin (8-OH-DPAT; 7.5 nmol, 50 nl) into the DRN led to a long-lasting reduction of the release rate of serotonin in the locus coeruleus. Microinjection of 8-OH-DPAT into the DRN also slightly lowered blood pressure (3 mmHg). Neither stimulations nor lesion of the DRN, nor microinjection of 8-OH-DPAT into this raphe nucleus, altered the extracellular concentration of 5-HIAA. Judging from the present biochemical results it appears that the serotonergic afferents to the locus coeruleus originate to more than 50% from cell bodies located in the DRN. The neuronal serotonin release in the locus coeruleus is modulated by 5-HT1A receptors lying within the DRN. Changes in blood pressure and release of serotonin elicited by stimulating or lesioning the DRN point to the importance of serotonergic neurons extending between this raphe nucleus and the locus coeruleus in central cardiovascular control.
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PMID:Dependence of serotonin release in the locus coeruleus on dorsal raphe neuronal activity. 1049 88

Pindolol and propranolol are used in the treatment of cardiovascular diseases, including hypotension or hypertension and antiarrythmic. Moreover, in the light of current 5-HT receptors classification it is known the mentioned drugs possess high 5-HT1A/5-HT1B affinity. It allows to establish two ways of researches. Department of Medicinal Chemistry of Medical University of Warsaw reports on synthesis of new compounds, analogues of Propranolol and Pindolol. A series of 5,8-dimethyl-3b,9-epoxy-3a,4,5,6,7,8,9,9a-octahydro-1H-benzo[e]isoindole-1,3(2H)-dione and 6,7-dimethyl-4,9-epoxy-3a,4,5,8,9,9a-hexahydro-1H-benzo[f]isoindole-1,3(2H)-dione have been designed with oxygen bridged rings. This property provides pharmacological activity increasing and toxicity decreasing.
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PMID:Synthesis of some N-substituted aminoalkanol derivatives of 5,8-dimethyl-3b,9-epoxy-3a,4,5,6,7,8,9,9a-octahydro-1H-benzo[e]isoindole-1,3(2H)-dione and 6,7-dimethyl-4,9-epoxy-3a,4,5,8,9,9a-hexahydro-1H-benzo[f]isoindole-1,3(2H)-dione with an expected b-adrenolytic activity. 1590 37


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