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 mixed beta-adrenoceptor and 5-HT1A receptor antagonists, (-)-pindolol and propranolol, enhance rather than inhibit the hyperlocomotion induced in rats by the 5-HT1A receptor agonist, 8-OH-DPAT. The mechanism of this effect was now investigated. The rats were pretreated with the beta-adrenoceptor antagonist or saline and with the agonist 45 min later. Ambulation was quantified as the number of quadrants entered during a 15 min observation period. (-)-Pindolol, alprenolol, betaxolol, ICI 118,551 and a combination of betaxolol and ICI 118,551 (all at 1 mg/kg) significantly enhanced the locomotion induced by 8-OH-DPAT (0.24 mg/kg). Timolol (1 and 10 mg/kg) given 45 min before 8-OH-DPAT was inactive; however, given at 10 mg/kg 15 min prior to 8-OH-DPAT, the compound enhanced locomotion. (-)-Pindolol (1 mg/kg) also enhanced the locomotion induced by the putative selective 5-HT1A receptor partial agonists, flesinoxan and ipsapirone, but not that induced by 5-OH-DPAT, a DA2 receptor agonist. These results suggest that beta 1- or beta 2-adrenoceptor antagonism can enhance the locomotion induced by 5-HT1A receptor agonists. In the case of mixed 5-HT1A and beta-adrenoceptor antagonists, the beta-adrenoceptor-mediated effect may mask the inhibition of locomotion expected from 5-HT1A receptor antagonism.
Eur J Pharmacol 1989 Dec 07
PMID:Beta-adrenoceptor blockade in rats enhances the ambulation induced by 5-HT1A receptor agonists. 257 26

The previous findings that the inducible [3H]-dihydroalprenolol (DHA) binding sites with low affinity for isoproterenol (RL) could be regulated by serotonin (5-HT) in vitro and by 5-hydroxytryptophan and the 5-HT uptake inhibitor fluoxetine in vivo, prompted the present pharmacologic characterization of these receptor sites, using nonlinear regression analysis of competition binding curves. If isoproterenol was used as the displacing agent, lesioning with 5,7-dihydroxytryptamine selectively increased [3H]-DHA binding sites with low micromolar affinity. By contrast, if 5-HT was used as the displacing agent, the receptor population with high agonist affinity showed a fourfold increase whereas the density of [3H]-DHA sites with low micromolar affinity for 5-HT was not altered. Neither the 5-HT1A agonist, 8-OH-DPAT, nor mianserin, a 5-HT2 and 5-HT1C antagonist, altered the induced RL receptor population, whereas the selective 5-HT1B agonist CGS-12066B reduced the increase in the RL receptor population with a potency equal to that of 5-HT. These results strengthen the notion that the [3H]-DHA sites with low agonist affinity for isoproterenol represent 5-HT1B receptors induced following a reduction of serotonergic neuronal function.
Neuropsychopharmacology 1989 Dec
PMID:Characterization of the inducible serotonin-sensitive dihydroalprenolol binding sites with low affinity for isoproterenol. 261 Aug 22

The systemic administration of the 5-HT1B receptor agonists, RU 24969 (0.25 and 0.5 mg/kg), TFMPP (0.25 and 0.5 mg/kg) and mCPP (0.75 and 1.0 mg/kg) resulted in an inhibition of rat masculine sexual behaviour reflected as a reduction in the proportion of copulating animals. Additionally, the analysis of the sexual behaviour of the animals obtaining ejaculation revealed that RU 24969 and TFMPP administration resulted in an increase in the number of mounts and in a prolongation of the intromission and ejaculation latencies and of the postejaculatory interval. Administration of mCPP increased the number of mounts preceding ejaculation. None of these changes could be attributed to a motor coordination impairment since none of these drugs, at the doses tested, produced changes in a treadmill test. The administration of the 5-HT1A agonist, ipsapirone (2.5, 5 and 10 mg/kg) resulted in a facilitation of the sexual behaviour expressed as a reduction in the number of intromissions preceding ejaculation accompanied by a shortening of the ejaculation latency. Present data show a differential action of 5-HT1A and 5-HT1B receptor subtypes in the control of rat masculine sexual behaviour. The hypothesis that the endogenous serotonin inhibitory action on copulation is mediated via the 5-HT1B receptor subtype is proposed.
Pharmacol Biochem Behav 1989 Dec
PMID:Inhibitory action of various 5-HT1B receptor agonists on rat masculine sexual behaviour. 262 35

The actions of NAN-190, a putative 5-HT1A antagonist, were assessed in rats. The selective 5-HT1A agent ipsapirone suppressed operant responding, but this effect was not antagonised by NAN-190, which suppressed responding itself in a dose-related manner, and had additive effects when administered with ipsapirone. These data do not support suggestions that NAN-190 is a 5-HT1A antagonist. NAN-190 may be a 5-HT1A partial agonist which can antagonise effects of full 5-HT1A agonists.
Pharmacol Biochem Behav 1989 Dec
PMID:In vivo interactions of NAN-190, a putative selective 5-HT1A antagonist, with ipsapirone. 262 48

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.
Br J Psychiatry Suppl 1989 Dec
PMID:Is there a relationship between serotonin receptor subtypes and selectivity of response in specific psychiatric illnesses? 269 41

Although suicide was traditionally considered an extreme response to stress, with the most frequent stress being depressive illness, severity of depression does not distinguish those who commit suicide from non-suicide attempters. A biological role involving the serotonergic system, possibly associated with a genetic risk factor, has been postulated. Low levels of 5-HT and 5-HIAA have been found in post-mortem examinations of brain-stem tissues of suicide victims (levels in cortical tissue were generally normal). An increased number of 5-HT2 receptors was found in the pre-frontal cortex of suicide victims, such upregulation having been demonstrated in induced 5-HT deficiency states; 5-HT1A receptors were also increased. Receptor populations may be altered by chronic psychotropic medication; e.g. 5-HT2 downregulation occurs following administration of antidepressants. There is some indication that the adrenergic system may be involved as well, but this will require further study. Antidepressant drugs may be effective in preventing suicide in patients with non-depressive syndromes who exhibit suicidal behaviour.
Br J Psychiatry Suppl 1989 Dec
PMID:Evidence for the 5-HT hypothesis of suicide. A review of post-mortem studies. 269 42

[3H]Dihydroergotamine (DE) labels a population of binding sites in rat brain membranes with an affinity of approximately 70 pM in both hippocampus (maximal binding at saturation [Bmax] = 340 fmol/mg of protein) and cerebral cortex (Bmax = 250 fmol/mg of protein). Specific binding typically comprises about 97% of total binding at the Kd of the radioligand when nonspecific binding is determined in the presence of 100 nM unlabeled DE. Association kinetics at 37 degrees C are consistent with a uniform association rate constant for all sites labeled. Specific binding is completely reversible with addition of excess unlabeled DE, but dissociation does not proceed with simple first-order kinetics, suggesting the presence of more than one discrete binding site. Competition studies with selective drugs reveal alpha adrenergic, 5-HT1A and 5-HT1B components of [3H]DE specific binding. When phentolamine (500 nM) is included to block alpha receptors and DPAT (100 nM) or spiroxatrine (500 nM) is included to block 5-HT1A receptors, specific binding is exclusively to sites with drug affinities characteristic of 5-HT1B receptors. Under these 5-HT1B-selective conditions, [3H]DE binding is about 90% specific, with a Kd of about 50 to 60 pM and a Bmax of 96 fmol/mg of protein in hippocampus and 77 fmol/mg of protein in cortex. [3H]DE binding to 5-HT1B sites is very slowly dissociable, with a T1/2 of greater than 2 h at 37 degrees C. 5-HT1B antagonists and DE itself yield competition curves at [3H]DE-labeled 5-HT1B sites that are adequately fit assuming a single site in nonlinear regression analysis. Competition by the agonists 5-HT and RU 24969 at 5-HT1B sites are often best described by two site fits. Addition of 100 microM guanylyl 5'-imidodiphosphate appears to convert nearly all 5-HT1B sites to those having low affinity for agonists while having a much smaller effect on the binding of [3H]DE. This suggests that the 5-HT1B site exists in two interconvertable agonist affinity states and is yet another member of the G-protein-linked receptor family. In agreement with previous studies using other radioligands, no 5-HT1B sites can be detected in bovine, porcine or human hippocampus membranes.
J Pharmacol Exp Ther 1987 Dec
PMID:[3H]dihydroergotamine as a high-affinity, slowly dissociating radioligand for 5-HT1B binding sites in rat brain membranes: evidence for guanine nucleotide regulation of agonist affinity states. 282 63

The mechanism responsible for the antihypertensive effect of urapidil is not yet completely understood. Its vasodilator action has been attributed to an antagonism at vascular alpha 1-adrenoceptors. However, it has been suggested that a central action contributes to the hypotensive effect. Recently, three potent analogues of urapidil have been described which also lower blood pressure by a central mechanism. 5-Hydroxytryptamine (5-HT) receptors of the 5-HT1A subtype have been implicated with the central control of cardiovascular function. In the present study, the affinities of these urapidil derivatives (5-acetyl, 5-formyl- and 5-methyl-urapidil) for 5-HT receptors were investigated using 3H-8-hydroxy-2-(di-n-propyl-amino)tetralin (3H-8-OH-DPAT), 125I-iodocyanopindolol (125I-ICYP) and 3H-ketanserin for labelling 5-HT1A, 5-HT1B and 5-HT2 binding sites, respectively. 3H-Prazosin and 3H-clonidine were used as selective alpha 1- and alpha 2-adrenoceptor radioligands, respectively. Urapidil and its analogues produced half-maximum inhibition of 3H-8-OH-DPAT binding at concentrations of 4 x 10(-9) mol/l to 4 x 10(-7) mol/l with the following order of potency: urapidil less than 5-acetyl- less than or equal to 5-formyl- less than 5-methyl-urapidil. Thus, 5-methyl-urapidil is one of the most potent ligands at 5-HT1A recognition sites known to date. The IC50 values of urapidil and its derivatives for 3H-prazosin binding were in the range of 5 x 10(-8) mol/l to 8 x 10(-7) mol/l (order of potency: urapidil less than 5-formyl- less than 5-acetyl- less than 5-methyl-urapidil).(ABSTRACT TRUNCATED AT 250 WORDS)
Naunyn Schmiedebergs Arch Pharmacol 1987 Dec
PMID:Urapidil and some analogues with hypotensive properties show high affinities for 5-hydroxytryptamine (5-HT) binding sites of the 5-HT1A subtype and for alpha 1-adrenoceptor binding sites. 283 70

A nonclassical 5-hydroxytryptamine (5-HT) receptor mediates the stimulation of adenylate cyclase activity in mouse embryo colliculi neurons in primary culture. The pharmacological profile characterized with agonists and antagonists suggests that this 5-HT receptor does not appear to correspond to a known 5-HT receptor. On this 5-HT receptor, 5-HT (EC50 = 109 +/- 17 nM) and 5-methoxytryptamine (5-MeOT) were equipotent agonists. The other tryptamine derivatives, 5-carboxamidotryptamine (5-CT) and 5-methoxy-N,N-dimethyltryptamine (5-MeOT-N,N-DMT), were full potent agonists, whereas tryptamine, bufotenine, and 2-CH3-5-HT were weak partial agonists. Two selective 5-HT1A agonists: 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) and ipsapirone, could not stimulate adenylate cyclase. RU 24969, a tetrahydropyridoindole derivative that is a potent 5-HT1A and 5-HT1B agonist was also inactive, whereas RU 28253, another member of this series, could stimulate cAMP production. The action of antagonists acting on 5-HT1 or 5-HT2 receptors, such as methiothepin (5-HT1 and 5-HT2), metergoline (5-HT1 and 5-HT2), spiperone (5-HT1A and 5-HT2), (-)-pindolol (5-HT1B), mesulergine (5-HT1C), and ketanserin (5-HT2), were almost inactive in reversing the 5-HT stimulating effect. The selective 5-HT3 antagonist ICS 205 930 was a full competitive antagonist at this receptor. Nevertheless, MDL 72222, which is also a 5-HT3 antagonist, was very weak in antagonizing the 5-HT stimulatory effect. A receptor with similar characteristics has also been found in guinea pig hippocampal membranes. In these membranes, the second receptor of low affinity for 5-HT, termed RL, which is positively coupled to adenylate cyclase, was also antagonized by ICS 205 930. The relatively low affinity of this hippocampal receptor for 5-CT, its stimulation by RU 28253 but not by RU 24969, and its previously reported pharmacological characteristics support the contention that this 5-HT receptor and the 5-HT receptor of mouse embryo colliculi neurons in primary culture (both positively coupled to cAMP formation) present great homologies. Inasmuch as none of the classical specific 5-HT1 and 5-HT2 agonists or antagonists interact with these 5-HT receptors, it is unlikely that they belong to 5-HT1 or 5-HT2 receptor categories.(ABSTRACT TRUNCATED AT 400 WORDS)
Mol Pharmacol 1988 Dec
PMID:A nonclassical 5-hydroxytryptamine receptor positively coupled with adenylate cyclase in the central nervous system. 284 52

1. The purpose of this study was to investigate the role of an intact baroreceptor reflex mechanism in the expression of the cardiovascular response to 8-OH-DPAT and to determine whether there are any differences between the activation of central alpha 2-adrenoreceptors and 5-HT1A receptors in this respect. To this end, the effects of 8-OH-DPAT and clonidine have been assessed on blood pressure, heart rate, ECG and cardiac contractility indices in conscious sino-aortic baroreceptor denervated (SAD) rats and their sham-operated controls. 2. In both sham-operated and SAD rats, intravenous (i.v.) administration of 8-OH-DPAT (32 micrograms kg-1) and clonidine (8 micrograms kg-1) produced falls in systemic blood pressure, left ventricular systolic pressure and dP/dtmax. 3. 8-OH-DPAT produced similar bradycardia in each group of rats; in contrast, clonidine had a greater effect in the SAD animals. Increases of the PQ interval mirrored the heart-rate changes with both compounds. 4. No significant changes in end diastolic blood pressure or in the myocardial contractility indices dP/dtmax/P and Vmax were evident. 5. This study provides support for the view that i.v. 8-OH-DPAT lowers blood pressure and heart rate through a central mechanism. The effects occur independently of an intact baroreceptor reflex and are not associated with effects on myocardial contractility. 8-OH-DPAT shows close qualitative similarities to clonidine in this model.
J Auton Pharmacol 1988 Dec
PMID:Comparison between the cardiovascular effects of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and clonidine in the conscious sino-aortic denervated rat. 285 30


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