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 effect of repeated administration of (+)-OXA (a noradrenaline (NA) uptake inhibitor) and (-)-OXA (devoid of an effect on the NA uptake, but a clinically active antidepressant drug) on central 5-HT receptor subpopulations was studied. (-)-OXA given repeatedly, but not acutely, attenuated the 8-OH-DPAT-induced hypothermia in mice. (+)-OXA administered acutely, as well as repeatedly, was inactive in that test. The 8-OH-DPAT-induced syndrome in rats was attenuated by both OXA isomers administered either acutely or repeatedly. The hypothermia induced by m-CPP in mice was attenuated by single-dose administration of (+)-OXA and (-)-OXA; when given repeatedly, (+)-OXA increased the action of m-CPP. (-)-OXA administered repeatedly was inactive in that test. Either single or repeated administration of (+)-OXA had practically no effect on the depression of exploratory activity induced by m-CPP. (-)-OXA administered acutely or repeatedly attenuated the effect of m-CPP in the same manner. Acute, but not chronic, administration of (-)-OXA reduced the number of head-twitch episodes induced by 5-HTP in mice. Repeated, but not acute, treatment with (+)-OXA attenuated the effect of 5-HTP. The obtained results indicate that (+)-OXA administered repeatedly increases the reactivity of 5-HT1B receptors, decreases the reactivity of 5-HT2 receptors, and has no effect on the reactivity of 5-HT1A- (pre- and postsynaptic) and 5-HT1C-receptors. (-)-OXA given repeatedly decreases the reactivity of presynaptic 5-HT1A receptors and has no influence on the reactivity of postsynaptic 5-HT1A-, 5-HT1B-, 5-HT1C- and 5-HT2-receptors.
Pol J Pharmacol
PMID:The effect of repeated treatment with oxaprotiline enantiomers on central 5-HT receptor subpopulations. 840 66

Effects of 5-HT receptor agonists (8-OH-DPAT, DOI and mCPP) on the binding parameters of corticosteroid receptors in the hippocampus of adult rats were studied. Glucocorticoid (GR) and mineralocorticoid (MR) receptors were examined by an in vitro [3H]corticosterone binding in cytosol, using the selective GR agonist RU 28362 to discriminate between MR and GR. Treatment with 8-OH-DPAT and mCPP given for 7 but not 1 days increased the density of MR. None of the compounds under investigation influenced the density of GR or the affinity of MR and GR in the rat hippocampus. Our results suggest that, in contrast to the postnatal period, the 5-HT1A and/or 5-HT2C, but not 5-HT2A, receptor is mainly involved in the regulation of MR in adult rats.
Pol J Pharmacol
PMID:Role of the serotoninergic system in the regulation of glucocorticoid and mineralocorticoid receptors in the rat hippocampus. 861 8

The effects of drugs selectively effecting central serotonergic systems on immobilization-induced analgesia (SIA) were tested in the rat. The drugs were used in dose ranges previously shown to effect emotional processes. SIA was tested using the tail withdrawal method. It was found that pretreatment of rats with para-chlorophenylalanine (p-CPA), an inhibitor of serotonin synthesis, significantly attenuated SIA, measured immediately after stress session. Ritanserin, a 5-HT2A/2C receptor antagonist, ondansetron, a 5-HT3 receptor antagonist and citalopram, a selective serotonin re-uptake blocker increased the baseline pain threshold, whereas 8-OH-DPAT, a full 5-HT1A receptor agonist and buspirone, a partial 5-HT1A receptor agonist expressing also high affinity towards dopaminergic D2 receptors, were without effect on pain perception and stress induced analgesia. It has been concluded, that modification of SIA by serotonergic drugs probably merely reflects changes in the activity of the 5-HT system on the spinal cord level, with minor, if any, contribution of supraspinal emotional centers.
Pol J Pharmacol
PMID:Influence of serotonergic drugs on restraint stress induced analgesia. 886 28

The receptor binding and pharmacological profile of the new, putative 5-HT1A receptor antagonist MP-3022 (4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine) were studied. Another 5-HT1A receptor antagonist, (S)-WAY 100135 ((S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2- phenylpropanamide), was used as a reference drug in functional models. MP-3022 showed a high affinity (Ki) of 25 nM and 69 nM, respectively, at 5-HT1A binding sites and alpha 1-adrenoceptors in vitro. The Ki values of MP-3022 in relation to other binding sites examined (5-HT2A, alpha 2- or beta-adrenoceptors, dopamine D1 and D2) were 20-100-fold lower. In functional studies, MP-3022 significantly attenuated the 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced decrease in the population spike evoked in the CA1 cell layer of the hippocampal slice preparation, without producing its own effects. The 8-OH-DPAT-evoked increase in the corticosterone concentration in the serum as well as the 8-OH-DPAT-mediated decrease in the 5-HT turnover in the hippocampus were attenuated by MP-3022. MP-3022 increased the serum corticosterone concentration only at the highest dose used, but it did not change the 5-HT turnover in the hippocampus. Like MP-3022, (S)-WAY 100135 antagonized the 8-OH-DPAT-induced effects. It has also been demonstrated that (S)-WAY 100135 is devoid of an intrinsic activity at 5-HT1A receptors. The data obtained demonstrate that, like (S)-WAY 100135, MP-3022 behaves like a functional antagonist at pre- and postsynaptic 5-HT1A receptors.
Pol J Pharmacol
PMID:MP-3022, a new putative antagonist at pre- and postsynaptic 5-HT1A receptors. 911 23

To date, more than two thousand experiments have investigated the behavioral effect of 5-HT-interacting drugs in animal models of anxiety disorders. Most of them have focused on the involvement of drugs interacting with 5-HT1A, 5-HT2A/2C and 5-HT3 receptors. Although numerous results are in line with the classic 5-HT hypothesis of anxiety, suggesting that decreased anxiety is related to decreased activity in central 5-HT neurons and vice versa, paradoxical drug effects have often been found. To explain this variability, several authors point to a determining role of the experimental paradigms used. In fact, an overview of the behavioral data arising from the vast literature indicates that conditioned procedures as well as more ethological-based tests are equal in revealing anxiolytic-like effects of drugs targetting 5-HT1A, 5-HT2A or 5-HT2C receptor subtypes. Furthermore, results obtained in ethologically-based animal models of anxiety with drugs stimulating 5-HT transmission are most consistent with the classic 5-HT hypothesis of anxiety in that they showed an increase in animals' emotional reactivity. Finally, anxiolytic-like effects of 5-HT3 receptor antagonists are in great part revealed by models based on spontaneous behaviors. Taken together, these observations lead to the conclusion that different 5-HT mechanisms, mediated by different receptor subtypes, are involved in the genesis of anxiety.
Pol J Pharmacol
PMID:Variability in the effects of 5-HT-related compounds in experimental models of anxiety: evidence for multiple mechanisms of 5-HT in anxiety or never ending story? 911 42

To examine the effects of 4-[3-(benzotriazol-1-yl)-propyl]-1-(2-methoxyphenyl)piperazine (MP-3022), a high affinity 5-HT1A ligand, on the 5-HT1A-induced stimulus effect and to compare its effects with those produced by some 5-HT1A receptor ligands, rats were trained to discriminate between 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 0.1 mg/kg ip, and saline in a standard, two-lever operant procedure. Substitution studies showed that the 8-OH-DPAT cue was mimicked in a dose-dependent manner by buspirone and ipsapirone, the 5-HT1A receptor partial agonists, but not by 1-(3-chlorophenyl)piperazine (m-CPP), a nonselective 5-HT agonist. Furthermore, the 8-OH-DPAT cue was almost completely blocked by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)]butylpiperazine (NAN-190), a 5-HT1A receptor and alpha 1-adrenoceptor antagonist, but not by prazosin (a selective alpha 1-adrenoceptor blocker). Our results also demonstrate that the discriminative effect of 8-OH-DPAT may be dose-dependently antagonized by MP-3022, which itself does not mimic the cue. It is concluded that MP-3022 behaves like a full 5-HT1A receptor antagonist in the 8-OH-DPAT-evoked discrimination procedure.
Pol J Pharmacol
PMID:Effects of MP-3022 on the 8-OH-DPAT-induced discriminative stimulus in rats. 911 79

Effects of repeated treatment with antidepressant drugs on the reactivity of CA1 neurons to 5-hydroxytryptamine (5-HT), (+/-)-8-hydroxy-2-(dipropyl-amino)-tetralin (8-OH-DPAT)--the 5-HT1A receptor agonist, and the zacopride-5-HT4 receptor agonist were examined in the rat hippocampus ex vivo. We sought to assess whether a presynaptic action of 5-HT receptor agonists on excitatory synaptic transmission contributed to the antidepressant-induced adaptive changes in responsiveness of pyramidal neurons to 5-HT1A and 5-HT4 receptor activation. The dendritic population excitatory postsynaptic potential (EPSP) evoked in the stratum radiatum of the CA1 region by stimulation of the Schaffer collateral-commissural pathway, was employed as a measure of the excitatory amino acid-mediated synaptic transmission, while the population spike recorded simultaneously in the CA1 cell layer was a measure of pyramidal cell excitability. 5-HT (10 microM) and 8-OH-DPAT (1 microM) decreased (by 40 +/- 5% and 30 +/- 7%, respectively), while zacopride (20 microM) increased (by 50 +/- 8%) the amplitude of the population spike. Neither drug had any effect on the slope of the population EPSP. The selective 5-HT1B receptor agonist CGS-12066 had no effect on the population spike or on the EPSP. Repeated treatment (14 days, twice daily, 10 mg/kg po) with imipramine and paroxetine augmented the inhibitory action of 5-HT on the population spike (by 50%), whereas treatment with citalopram and fluvoxamine had no effect. Imipramine and paroxetine, but not fluvoxamine, increased the 8-OH-DPAT-induced inhibition (by 80-100%). All of the antidepressant drugs studied attenuated the excitatory effect of zacopride on the population spike (by 70%). The population EPSPs in slices from rats treated with antidepressant drugs were not affected by 5-HT, 8-OH-DPAT or zacopride. It has been concluded that adaptive changes in the responsiveness of CA1 cells to 5-HT, 8-OH-DPAT and zacopride, induced by repeated administration of antidepressant drugs do not involve presynaptic effects on excitatory synaptic transmission.
Pol J Pharmacol
PMID:Antidepressant-induced adaptive changes in the effects of 5-HT, 5-HT1A and 5-HT4 agonists on the population spike recorded in hippocampal CA1 cells do not involve presynaptic effects on excitatory synaptic transmission. 911 95

Thirty eight years after the successful clinical introduction of antidepressant agents, there has been an important progress in the knowledge and changes in thinking about the role of central serotonergic system in depression and in the mechanism of their therapeutic efficacy. Although it is not clear whether an increase or decrease in serotoninergic function is more important in antidepressant action of agents, there is increasing evidence that almost all antidepressant drugs can induce changes in the sensitivity of somotodendritic 5-HT1A autoreceptors and postsynaptic 5-HT2 receptors in spite of very different pharmacological profiles after a single administration. The question arises as to the causal nature of the relationship between these effects and beneficial clinical action. Further studies are still required to dispel these doubts.
Psychiatr Pol
PMID:[The role of serotonergic system in the mechanism of action of antidepressant agents]. 913 70

The behavioral and biochemical effects of EMD 57445, a selective sigma receptor ligand with potential antipsychotic activity, on the 5-hydroxytryptamine (5-HT) system were studied in rats and mice. The drug influence was investigated in three behavioral tests: 8-OH-DPAT (5-HT1A agonist)-induced behavioral syndrome in rats, m-chlorophenylpiperazine (m-CPP, 5-HT1B agonist)-induced hypothermia in mice and L-5-hydroxytryptophan (L-5-HTP)-induced head twitches (5-HT2A stimulation) in rats. EMD 57445 did not show any activity in all three behavioral models. In biochemical studies, no changes in the 5-HT and 5-HIAA levels in rat brain cortex, nucleus accumbens, striatum, hypothalamus and hippocampus were found. The results indicate that EMD 57445 does not interact with 5-HT (5-HT1A, 5-HT1B, 5-HT2A) receptor subpopulations and does not affect 5-HT metabolism.
Pol J Pharmacol
PMID:EMD 57445, the selective sigma receptor ligand, has no effect on the 5-hydroxytryptamine system. 956 54

In continuation of the development of antipsychotic and anxiolytic agents with a reduced propensity toward extrapyramidal side-effects, a series of N-aminoalkyl derivatives of (s)-(+)-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11-(10H, 11aH)-dione was prepared. Evaluation of these compounds in revealed a very low affinity for 5-HT1A receptor.
Acta Pol Pharm
PMID:Synthesis of new N-substituted benzodiazepine derivatives with potential anxiolytic activity. 960 96


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