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)

TVX Q 7821 is a putative non-benzodiazepine anxiolytic which has a high affinity to 5-HT1 receptors. In this study some of the binding characteristics of the radiolabeled drug using rat brain cryostat sections and the autoradiographic localization of binding sites using the LKB-Ultrofilm technique have been investigated. Parallel experiments have been performed using [3H]serotonin ( [3H]5-HT). Both [3H]TVX Q 7821 and [3H]5-HT bound specifically and in a saturable manner to tissue sections, the Kd values being 6.8 and 3.7 nmol/l, respectively. Quantitative autoradiography using computer-assisted image analysis revealed a mean inhibition by TVX Q 7821 of [3H]5-HT binding of 56% in many brain areas. The inhibition ranged from 80% in the hippocampus and entorhinal area to practically none in the substantia nigra and the dorsal subiculum. Color coded autoradiograms obtained either with [3H]5-HT or [3H]TVX Q 7821 showed a nearly identical pattern of labeling with high receptor densities in the hippocampus, the entorhinal area, the septum, the interpeduncular nucleus and the dorsal raphe. However, in some brain areas striking differences in the intensity of labeling were found. [3H]5-HT but not [3H]TVX Q 7821 bound strongly in the substantia nigra, the dorsal subiculum and the globus pallidus. It is proposed that TVX Q 7821 binds to a subtype of 5-HT1 receptor (the so-called 5-HT1A sites as recently proposed). Thus, the putative anxiolytic TVX Q 7821 may provide a means for the study of the functional role of 5-HT1 receptors.
Brain Res 1985 Dec 09
PMID:Autoradiographic identification and topographical analyses of high affinity serotonin receptor subtypes as a target for the novel putative anxiolytic TVX Q 7821. 286 16

In the presence of a 30 nM prazosin mask, [3H]-2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane ([3H]WB4101) can selectively label 5-HT1 serotonin receptors. Serotonin exhibits high affinity (Ki = 2.5 nM) and monophasic competition for [3H] WB4101 binding in cerebral cortex. Furthermore, we have found a significant correlation (r = 0.96) between the affinities of a number of serotonergic and nonserotonergic compounds at [3H]WB4101-binding sites in the presence of 30 nM prazosin and [3H] lysergic acid diethylamide ([3H]LSD)-labeled 5-HT1 serotonin receptors in homogenates of rat cerebral cortex. Despite similar pharmacological profiles, distribution studies indicate that, in the presence of 5 mM MgSO4, the Bmax of [3H]WB4101 is significantly lower than the Bmax of [3H]LSD in various brain regions. WB4101 competition for [3H] LSD-labeled 5-HT1 receptors fits best to a computer-derived model assuming two binding sites, with the KH for WB4101 being similar to the KD of [3H]WB4101 binding derived from saturation experiments. This suggests that [3H]WB4101 labels only one of the subtypes of the 5-HT1 serotonin receptors labeled by [3H]LSD. Interestingly, the selective 5-HT1A serotonin receptor antagonist, spiperone, and the selective 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetraline, exhibit high affinity and monophasic competition for [3H]WB4101 but compete for multiple [3H]LSD 5-HT1 binding sites. These data indicate that [3H]WB4101 selectively labels the 5-HT1A serotonin receptor, whereas [3H] LSD appears to label both the 5-HT1A and the 5-HT1B serotonin receptor subtypes. The divalent cations, Mn2+, Mg2+, and Ca2+ were found to markedly increase the affinity and Bmax of [3H]WB4101 binding in cerebral cortex. Conversely, the guanine nucleotides guanylylimidodiphosphate and GTP, but not the adenosine nucleotide ATP, markedly reduce the Bmax of [3H]WB4101 binding. These characteristics are typical of agonists interacting with receptors which modulate cellular function via a guanine nucleotide-regulatory subunit.
Mol Pharmacol 1985 Dec
PMID:[3H]WB4101 labels the 5-HT1A serotonin receptor subtype in rat brain. Guanine nucleotide and divalent cation sensitivity. 286 62

The neurophysiological effects of two novel anxiolytic compounds, buspirone and isapirone (TVX Q 7821), were compared with those of 5-hydroxytryptamine (5-HT) on the population spike in the CA1 region of the rat hippocampal slice. Micromolar concentrations of the two drugs mimicked the inhibitory effect of 5-HT but unlike 5-HT they did not produce any significant excitation. In slices in which 5-HT was purely excitatory, there was a marked reduction in the inhibitory response to these agents. The effect of isapirone was antagonised by spiperone. These results suggest that buspirone and isapirone are agonists for 5-HT1A receptors in the hippocampus.
Eur J Pharmacol 1986 Dec 02
PMID:Neurophysiological effects of buspirone and isapirone in the hippocampus: comparison with 5-hydroxytryptamine. 288 Jul 31

Ipsapirone and gepirone, but not buspirone, facilitated lordosis in estrogen-treated rats, whereas all three drugs inhibited this behavior in rats treated with estrogen and progesterone. When administered at higher doses, ipsapirone, gepirone and buspirone inhibited lordosis in rats treated with either estrogen or estrogen and progesterone. These data are consistent with the proposal that 5-HT1A receptors mediate lordosis-inhibiting effects of 5-HT, and further suggest that some 5-HT1A agonists may facilitate lordosis by activity at autoreceptors. Finally, these data show that progesterone may modulate activity at 5-HT1A receptors.
Eur J Pharmacol 1986 Dec 16
PMID:Effects of 5-HT1A selective anxiolytics on lordosis behavior: interactions with progesterone. 288 Jul 37

Local cerebral glucose utilization (LCGU) was measured in the hippocampus of the rat brain following i.p. injection of the anxiolytic drug and 5-HT1A receptor agonist ipsapirone (TVX Q 7821). Administration of ipsapirone (5 mg/kg) reduced glucose utilization in the various hippocampal areas to variable extent. The most subtle reduction took place in the dorsal subiculum, while the most pronounced decrease was found in sector CA4 of Ammon's horn. The degree of LCGU reduction can be related to the 5-HT1A receptor density in the respective areas.
Brain Res 1987 Dec 15
PMID:Effect of the 5-HT1A receptor agonist ipsapirone on the local cerebral glucose utilization of the rat hippocampus. 289 52

The binding of [3H]8-hydroxy-2-(di-N-propylamino)-tetralin ([ 3H]8-OH-DPAT) to rat hippocampal and striatal membranes has been compared. In the hippocampus, low concentrations of [3H]8-OH-DPAT bound to a single, high affinity site which was sensitive to inhibition by spiperone, buspirone and ergotamine but not by mianserin, quipazine or (-)-propranolol. This is consistent with a selective labeling of the 5-HT1A receptor. In the striatum, [3H]8-OH-DPAT bound to two sites with high and low affinity (KD's 1.18 and 109 nM). The high affinity component was blocked by low concentrations of buspirone, spiperone and ergotamine. The low affinity component was blocked only by high concentrations of buspirone and spiperone, and was not displaced by ergotamine at concentrations up to 1 microM. The ergotamine-resistant component of striatal [3H]8-OH-DPAT binding was blocked by low concentrations of the 5-HT uptake inhibitors fluvoxamine and paroxetine, and by relatively low concentrations of 5-HT itself. Thus [3H]8-OH-DPAT labels the 5-HT transporter in the rat striatum. Unlike [3H]imipramine binding, the binding of [3H]8-OH-DPAT to the 5-HT transporter was independent of external sodium ions. It is therefore suggested that 8-OH-DPAT acts as substrate for the 5-HT transporter and labels the 5-HT recognition site of the transporter complex.
J Pharm Pharmacol 1988 Dec
PMID:[3H]8-OH-DPAT labels the 5-hydroxytryptamine uptake recognition site and the 5-HT1A binding site in the rat striatum. 290 86

RDS-127, in a dose-related manner, induced seminal emission ex copula after intracerebroventricular (i.c.v.) administration. In mating tests initiated 6 min after i.c.v. administration, RDS-127 induced decreases in ejaculation latency and intromission frequency, with some rats ejaculating on the initial intromission. Additionally, penile reflexes were eliminated by 150 micrograms and 600 micrograms, but not by an intermediate dose. In in vitro radioligand binding studies, RDS-127 potently displaced [3H]DPAT binding to 5-HT1A sites in rat cortex (Ki = 14 +/- 4 nM) and was only moderately effective in displacing [3H]spiperone binding to dopaminergic D2 sites in rat striatum. RDS-127 was essentially ineffective at 5-HT1B sites labeled by [3H]5-HT in rat striatum (Ki = 13 000 +/- 4 000 nM). These data demonstrate that centrally administered RDS-127 mimics the previously reported alterations in sexual behavior after systemic treatment and that RDS-127 is a high affinity 5-HT1A agent with low affinity at the 5-HT1B binding site.
Behav Brain Res 1985 Dec
PMID:Central effects of RDS-127: sexual behavior after intracerebroventricular administration and in vitro receptor binding studies. 293 65

We measured the inhibition of forskolin-stimulated adenylate cyclase activity in guinea pig hippocampal membranes by 5-HT, 5-carboxamidotryptamine (CAT) and 8-hydroxy-2-(di-n-propylamino) tetralin (PAT). Low concentrations of these agonists inhibited forskolin-stimulated adenylate cyclase activity in a concentration-dependent and saturable manner. The antagonist spiperone shifted the concentration-response curve to CAT to the right in a parallel manner. The EC50 values of CAT, PAT and 5-HT and the KB of spiperone suggest that this receptor may correspond to the 5-HT1A binding site.
Eur J Pharmacol 1985 Dec 17
PMID:Inhibition of forskolin-stimulated adenylate cyclase activity by 5-HT receptor agonists. 293 12

The distribution of the 2 main types (A and B) of 5-HT1 binding sites in the rat brain was studied by light-microscopic quantitative autoradiography. The 5-HT1A sites were identified using 3H-8-hydroxy-2-(N-dipropylamino)tetralin (3H-8-OH-DPAT) or 3H-5-HT as the ligand. In the latter case, it was shown that 3H-5-HT binding to 5-HT1A sites corresponded to that displaceable by 0.1 microM 8-OH-DPAT or 1 microM spiperone. The "non-5-HT1A" sites labeled by 3H-5-HT in the presence of 0.1 microM 8-OH-DPAT corresponded mainly to 5-HT1B sites. 5-HT1A binding was notably high in limbic regions (dentate gyrus, CA1 and CA3 hippocampal regions, lateral septum, frontal cortex), whereas 5-HT1B binding was particularly concentrated in extrapyramidal areas (caudate nucleus, globus pallidus, substantia nigra). Except in the latter regions, where only one class of 5-HT1 sites was found, both 5-HT1A and 5-HT1B sites existed in all areas examined. The selective degeneration of serotoninergic neurons produced by an intracerebral injection of 5,7-dihydroxytryptamine was associated only with a significant loss of 5-HT1A binding to the dorsal raphe nucleus (-60%) and of 5-HT1B binding to the substantia nigra (-37%). These results are discussed in relation to the possible identity of 5-HT1A and/or 5-HT1B sites with the presynaptic 5-HT autoreceptors controlling nerve impulse flow and neurotransmitter release in serotoninergic neurons.
J Neurosci 1986 Dec
PMID:Quantitative autoradiography of multiple 5-HT1 receptor subtypes in the brain of control or 5,7-dihydroxytryptamine-treated rats. 294 81

The effects of serotonergic agonists and antagonists on the body temperatures of rats were investigated. The administration of the serotonin (5-HT) agonist 6-chloro-2(1-piperazinyl)-pyrazine (MK-212) produced a dose-related increase in body temperature. A maximal increase in body temperature of approx. 1.1 degrees C was observed 30 min after the administration of 3 mg/kg of MK-212. In contrast, administration of the putative 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) resulted in marked, dose-related hypothermic responses. Body temperatures were decreased approx. 3 degrees C 30 min after an injection of 0.3 mg/kg of 8-OH-DPAT. Body temperatures were affected differentially by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT). Large doses (3-10 mg/kg) of 5-MeODMT elicited hyperthermic responses, whereas small doses (0.5-1.0 mg/kg) produced hypothermic responses. Treatment of rats with ketanserin (3 mg/kg) completely prevented the hyperthermic effects of 5-MeODMT, and, in fact, converted a hyperthermic response to 5-MeODMT into a marked hypothermic response. Ketanserin (0.1-1.0 mg/kg) selectively antagonized the hyperthermic response to MK-212 but did not alter the hypothermic effect of 8-OH-DPAT. Mianserin (10 mg/kg) and pirenperone (0.03 mg/kg) also selectively antagonized hyperthermia induced by MK-212. In contrast, pindolol (0.03-0.1 mg/kg) and methiothepin (10 mg/kg) selectively antagonized hypothermia induced by 8-OH-DPAT but did not alter hyperthermia induced by MK-212. Spiperone (0.1-3 mg/kg) and pizotifen (10 mg/kg) attenuated the effects of both 8-OH-DPAT and MK-212. Xylamidine, a peripheral 5-HT antagonist, had no significant effect on hyperthermia induced by MK-212 or hypothermia induced by 8-OH-DPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuropharmacology 1986 Dec
PMID:Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat. Evidence for opposing roles of 5-HT2 and 5-HT1A receptors. 295 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>