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 effects of MDL 73005EF (8-[2-(2,3-dihydro-1,4-benzodioxin-2-yl)methylamino]-8- azaspiro[4,5]decan-7,9-dione methyl sulphonate), a novel selective 5-HT1A receptor ligand with putative anxiolytic properties, were explored using models of central pre- and postsynaptic 5-HT1A receptor function in the male rat. MDL 73005EF dose dependently decreased the hippocampal 5-HT output measured by in vivo microdialysis in chloral hydrate-anaesthetised rats and this response was antagonised by the 5-HT1A/B receptor antagonist, pindolol. Local administration of MDL 73005EF had no effect on the hippocampal 5-HT output. MDL 73005EF failed to alter basal plasma adrenocorticotropin (ACTH) levels but, in common with pindolol, attenuated the ACTH response to the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). In contrast to 8-OH-DPAT, MDL 73005EF significantly increased plasma prolactin but apparently not through a 5-HT receptor-mediated mechanism. The results indicate that MDL 73005EF possesses mixed 5-HT1A receptor agonist/antagonist properties, acting as an agonist at presynaptic 5-HT1A receptors controlling 5-HT release and as an antagonist at postsynaptic 5-HT1A receptors mediating ACTH release.
Eur J Pharmacol 1990 Dec 04
PMID:Effects of MDL 73005EF on central pre- and postsynaptic 5-HT1A receptor function in the rat in vivo. 196 8

The present study employed various receptor-binding assays to clarify the biochemical characteristics of SM-9018. SM-9018 possessed very high affinity for 5-HT2, D2 and 5-HT1A receptors (Ki = 0.61, 1.4 and 2.9 nM, respectively), and it had moderate affinity for alpha 1 and D1 receptors (Ki = 17 and 41 nM, respectively). However, SM-9018 had only negligible affinity for alpha 2, opiate, glutamate, phencyclidine, benzodiazepine and GABAA receptors. These results suggest that SM-9018 may be a novel antipsychotic agent with binding affinity for 5-HT2 and 5-HT1A receptors.
Jpn J Pharmacol 1990 Dec
PMID:Binding profile of SM-9018, a novel antipsychotic candidate. 198 26

The ability of selective and nonselective 5-HT1A agonists, nondirect 5-HT agonists and 5-HT2 antagonists influence on the L-DOPA-disturbed rats behaviour were studied. The results indicate that agonists 5-HT1A like receptors largely than 5-HT2,3 agonists, 5-HT2 antagonists and nondirect 5-HT agonists promote restoration of the L-DOPA disturbed escape behaviour in acute stress situation.
Biull Eksp Biol Med 1990 Dec
PMID:[The agonists of I-A serotoninergic receptors restore in rats behavior impaired by L-dihydroxyphenylalanine]. 208 66

We conducted the present study to investigate the effects of 5-hydroxytryptamine agonists on brain morphology after the induction of focal cerebral ischemia by permanent occlusion of the left middle cerebral artery in rats and mice. Forty-eight hours after vessel occlusion, the damage was quantified in rats by planimetry and subsequent integration on cresyl violet-stained serial sections and in mice by planimetric analysis of the damaged cortical surface after counterstaining with carbon black. All 5-HT1A agonists investigated substantially decreased cortical infarct size in the rat focal ischemia model (p less than 0.05). Drugs were applied 30 minutes before the induction of ischemia, and efficacy was demonstrated for 8-OH-DPAT (1 mg/kg s.c.), buspirone (10 mg/kg i.p.), gepirone (10 mg/kg i.p.), ipsapirone (10 or 30 mg/kg i.p.), and Bay R 1531 (1 mg/kg i.p.). The most pronounced effects were seen with the higher dose of ipsapirone and Bay R 1531, both compounds reducing cortical infarct size by more than 60%. Except for 8-OH-DPAT, the 5-HT1A agonists also caused a reduction in total infarct volumes. In a separate series, ipsapirone (30 mg/kg i.p.), applied 1 hour after vessel occlusion, led to a reduction in cortical and total infarct volumes by about 50% compared with corresponding controls (p less than 0.05). In neither series was striatal damage influenced. We tested the compounds in the mouse ischemia model over a broad dose range.(ABSTRACT TRUNCATED AT 250 WORDS)
Stroke 1990 Dec
PMID:5-hydroxytryptamine1A agonists. A new therapeutic principle for stroke treatment. 214 35

The activation of 5-hydroxytryptamine receptors exerts an inhibitory influence on neuronal activity in a way similar to the activation gamma-amino-n-butyric acid and adenosine A1 receptors. Therefore, we hypothesized that 5-HT1A-receptor agonists might exert a neuroprotective effect. We tested the full agonists Bay R 1531 and 8-OH-DPAT and the partial agonists ipsapirone and gepirone in the model of transient global ischemia in the Mongolian gerbil. Ipsapirone protected 53% of pyramidal neurons (p less than 0.05) in the CA1 area of the hippocampus from ischemic damage at a dose of 3 mg/kg. Bay R 1531 showed a powerful neuroprotective effect with 100% preservation of neurons at a dose of 3 mg/kg (p less than 0.001) while gepirone and 8-OH-DPAT were ineffective. These findings suggest that 5-HT1A-receptor agonists might be effective tools for the therapy of cerebral ischemia. However, the varying results indicate that transient forebrain ischemia in the gerbil may not be the optimal model system to demonstrate clearly the neuroprotective activity of these compounds.
Stroke 1990 Dec
PMID:Effects of 5-hydroxytryptamine1A-receptor agonists on hippocampal damage after transient forebrain ischemia in the Mongolian gerbil. 214 36

The role of the 5-hydroxytryptamine (5-HT) receptor subtypes in the spinal cord in the regulation of nociception is unknown. This study examined whether administration of different 5-HT1 receptor agonists into the spinal subarachnoid space of mice modulates the nociceptive tail-flick reflex, and whether effects on the tail-flick reflex involve changes in tail skin temperature. The tail-flick latencies (the time needed to evoke the tail-flick reflex by noxious radiant heat) were significantly increased after intrathecal (i. th.) injection of 5-HT (10-20 micrograms), the 5-HT1A/5-HT1B receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 10-20 micrograms), the selective 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 20 micrograms) and after i.th. injection of 1(m-chlorophenyl)piperazine (mCPP, 5-20 micrograms) and 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole (RU 24969, 5-20 micrograms) which have high affinity for the 5-HT1B receptors. None of the 5-HT1 receptor agonists had the ability to change the tail skin temperature. The results show that in the mouse i.th. injection of both 5-HT1A and 5-HT1B receptor agonists has the ability to inhibit the tail-flick reflex without interfering with the tail skin temperature.
Brain Res 1990 Dec 17
PMID:The role of spinal cord 5-HT1A and 5-HT1B receptors in the modulation of a spinal nociceptive reflex. 215 Jul 69

Activation of serotonergic neurotransmission has been shown to increase plasma beta-endorphin-like immunoreactivity (beta-End-LI). To study the mechanism(s) of this action, we measured the effects of 3 potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles in conscious unrestrained Sprague-Dawley rats in vivo and in dispersed anterior pituicytes in vitro. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), all markedly increased beta-End-LI in plasma in vivo. All 3 responses were blocked by dexamethasone pretreatment. Pituitary stalk transection (PST), as well as pretreatment with rabbit serum hyperimmune against rat corticotropin-releasing hormone (CRH, TS-6) completely abolished beta-End-LI response to 8-OH-DPAT and attenuated the responses by about 60% to DOI. Responses to m-CPP were markedly attenuated in PST rats, but pretreatment with TS-6 had no significant effect. To examine whether vasopressin (AVP) might be involved in the CRH neutralizing antibody-resistant beta-End-LI responses after m-CPP and DOI, we measured AVP concentrations after each agonist, m-CPP, but not DOI or 8-OH-DPAT, significantly elevated circulating AVP levels. As a proof of direct pituitary effect, DOI markedly stimulated beta-End-LI release from the anterior pituitary cell culture preparation in vitro. It was approximately as potent as CRH in the picomolar range, m-CPP was much less effective than DOI, while 8-OH-DPAT did not stimulate beta-End-LI release in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res 1990 Dec 24
PMID:Beta-endorphin responses to different serotonin agonists: involvement of corticotropin-releasing hormone, vasopressin and direct pituitary action. 215 Jul 76

Selective 5-HT1A receptor agonists such as 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), flesinoxan, 5-methylurapidil and others, increased locomotor behaviour in rats following s.c. injection. Unfortunately, all available 5-HT1A receptor antagonists are non-selective, a fact which severely hampers their use. The inhibitory effects of (+)- and (-)-pindolol (1-10 mg/kg, -45 min s.c.) on locomotion induced by 8-OH-DPAT were investigated in rats pretreated with the beta-adrenoceptor antagonists, ICI 118,551 and betaxolol (both 1 mg/kg, -45 min s.c.). ICI 118,551 and betaxolol significantly enhanced the response to 8-OH-DPAT. Co-administration of (-)-pindolol (2-10 mg/kg) dose dependently antagonised the hyperlocomotion whereas (+)-pindolol was weakly effective at 10 mg/kg. The partial agonists ipsapirone (1-10 mg/kg, -45 min s.c.) and buspirone (0.1-1 mg/kg, -45 min) antagonised the effects of 8-OH-DPAT. This inhibition may, however, be due to alpha 1-adrenoceptor blockade and DA receptor antagonism, respectively. Finally, although spiroxatrine (0.1 and 1 mg/kg, -45 min s.c.) inhibited the response to 8-OH-DPAT, this inhibition may also be non-specific since spiroxatrine strongly reduced spontaneous locomotor activity. In conclusion, whilst much of our data is consistent with 8-OH-DPAT-induced locomotion being mediated by 5-HT1A receptors, only the data obtained with the pindolol enantiomers provide direct evidence for this. The results also suggest that, under normal circumstances, the 5-HT1A receptor antagonist effect of pindolol may be masked by the facilitating effect of beta-adrenoceptor blockade.
Eur J Pharmacol 1990 Dec 04
PMID:Determination of the 5-HT receptor subtype involved in 8-OH-DPAT-induced hyperlocomotion: potential difficulties arising from inadequate pharmacological tools. 215 Aug 21

Tiflucarbine is a structurally novel antidepressant that binds at central serotonin (5-HT) binding sites. There is also evidence that this agent is both a 5-HT1 and a 5-HT2 agonist. To further characterize the serotonergic actions of this agent, tiflucarbine was evaluated in groups of rats trained to discriminate the 5-HT1A agonist 8-OH DPAT, the 5-HT2 agonist DOM, and the nonselective 5-HT agonist 5-OMe DMT from saline. Tiflucarbine resulted in partial generalization in the DOM-trained and in the 8-OH DPAT-trained animals. Although two-thirds of the animals were disrupted, 10 mg/kg of tiflucarbine resulted in stimulus generlization in the 5-OMe DMT-trained animals. It is concluded that tiflucarbine is most likely a nonselective 5-HT agonist.
Pharmacol Biochem Behav 1990 Dec
PMID:Stimulus properties of tiflucarbine: a novel antidepressant agent. 215 Nov 99

Agonist occupancy of the cloned human serotonin (5-HT)1A receptor expressed in HeLa cells stimulates Na+/K+ ATPase activity as assessed by rubidium uptake. The purpose of the study was to determine which of the receptor-associated signaling mechanisms was responsible for this effect. 5-HT stimulated Na+/K+ ATPase 38% at 2 mM extracellular potassium, an effect characterized by a decrease in apparent K0.5 from 2.8 +/- 0.3 to 1.8 +/- 0.3 mM potassium without a significant change in apparent Vmax. The EC50 for the transport effect was approximately 3 microM 5-HT. The response was pertussis toxin-sensitive but did not involve inhibition of adenylate cyclase, as stimulation of Na+/K+ ATPase by 5-HT was observed in the presence of excess dibutyryl cAMP. Protein kinase C was not required for the response since short-term incubation with the phorbol esters phorbol 12 myristate, 13 acetate (PMA) and phorbol 12,13-dibutyrate (PDBu) did not mimic the 5-HT effect. Moreover, 5-HT increased Na+/K+ ATPase activity after inactivation of protein kinase C by overnight incubation with PMA. 5-HT and the sesquiterpene lactone thapsigargin increased cytosolic calcium in this cell model, and the EC50 for 5-HT corresponded with that for stimulation of Na+/K+ ATPase. Both thapsigargin and A23187, a calcium ionophore, also increased Na+/K+ ATPase activity in a dose-responsive fashion. The response to 5-HT, thapsigargin, and A23187 was blocked by conditions that removed the cytosolic calcium response. By two-dimensional gel electrophoresis, we established evidence for a calcium-sensitive but protein kinase C-independent signaling pathway. We conclude that the 5-HT1A receptor, which we have previously shown to stimulate phosphate uptake via protein kinase C, stimulates Na+/K+ ATPase via a calcium-dependent mechanism. This provides evidence for regulation of two separate transport processes by a single receptor subtype via different signaling mechanisms.
J Clin Invest 1990 Dec
PMID:Short-term regulation of Na+/K+ adenosine triphosphatase by recombinant human serotonin 5-HT1A receptor expressed in HeLa cells. 217 7


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