Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine—II. Effects of acute administration of 1-PP and long-term adminstration of tandospirone on noradrenergic neurotransmission

@article{Blier1991TandospironeAI,
  title={Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine—II. Effects of acute administration of 1-PP and long-term adminstration of tandospirone on noradrenergic neurotransmission},
  author={Pierre U. Blier and Olivier Louis Curet and Yves JA Chaput and Claude de Montigny},
  journal={Neuropharmacology},
  year={1991},
  volume={30},
  pages={691-701}
}
1-(2-Pyrimidinyl)-piperazine (1-PP) is a common metabolite of the antidepressant/anxiolytic 5-HT1A agonists, tandospirone (SM-3997), gepirone, buspirone and ipsapirone. The present electrophysiological studies were undertaken to characterize in vivo the effect of 1-PP on noradrenergic (NE) neurotransmission in rat brain. At small doses, 1-PP (ED50 = 80 micrograms/kg, i.v.) reversed the depressant effect of the alpha 2-adrenoceptor agonist, clonidine (20 micrograms/kg, i.v.) on the firing… Expand
Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine—I. Effects of acute and long-term administration of tandospirone on serotonin neurotransmission
TLDR
It is concluded that desensitization of somatodendritic 5-HT autoreceptors permits5-HT neurones to regain their physiological rate of firing during long-term treatment with tandospirone and, consequently, to release a normal amount of 5- HT into the synaptic cleft. Expand
The azapirone metabolite 1-(2-pyrimidinyl)piperazine depresses excitatory synaptic transmission in the hippocampus of the alert rat via 5-HT1A receptors.
TLDR
The effects of acute and repeated treatment with 1-(2-pyrimidinyl)piperazine (1-PP), a metabolite of the 5-HT1A receptor ligand azapirones, were investigated on hippocampal excitatory synaptic transmission to indicate that the previously reported reduction in the e.p.s.s.'s may be mediated in part by their metabolite 1-PP through activation of 5- HT1A receptors. Expand
Evaluation of the alpha 2-adrenoceptor blocking properties of buspirone and ipsapirone in healthy subjects. Relationship with the plasma concentration of the common metabolite 1-(2-pyrimidinyl)-piperazine.
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In vivo comparison of two 5-HT1A receptors agonists alnespirone (S-20499) and buspirone on locus coeruleus neuronal activity.
TLDR
Alnespirone is devoid in vivo of significant alpha(2)-adrenoceptor antagonist properties, in contrast with some aryl-piperazine compounds (such as buspirone). Expand
Effects of tandospirone on second messenger systems and neurotransmitter release in the rat brain.
TLDR
It is suggested that tandospirone shows high agonistic efficacy on the postsynaptic 5-HT1A receptors but does not affect the presynaptic autoreceptors located on nerve endings, which might be involved in the anxiolytic efficacy of tandspirone. Expand
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TLDR
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TLDR
Prolonged administration of (+/-)pindolol by itself is not sufficient to enhance overall 5-HT neurotransmission; pindoll should therefore not be endowed with intrinsic antidepressant activity. Expand
Tandospirone suppresses impulsive action by possible blockade of the 5-HT1A receptor.
TLDR
Tandospirone could be a therapeutic candidate for impulsivity-related disorders and may be due to the antagonistic action of the 5-HT1A receptor. Expand
Effect of sustained administration of the 5-HT1A receptor agonist flesinoxan on rat 5-HT neurotransmission
TLDR
As for selective 5- HT re-uptake inhibitors, monoamine oxidase inhibitors and 5-HT1A receptor agonists, flesinoxan produced most of the adaptive changes exerted by these antidepressant drugs on the 4-HT system and the marked potency and the long dissociation constant of fles inoxan for the 5-ht1A receptors may account for the latter discrepancy. Expand
Tandospirone activates neuroendocrine and ERK (MAP kinase) signaling pathways specifically through 5-HT1A receptor mechanisms in vivo
TLDR
The results are the first evidence that systemic 5-HT1A receptor agonist administration produces a rapid increase in p-ERK levels in vivo, providing further insight into the signaling mechanisms of the 5- HT1A receptors. Expand
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Tandospirone and its metabolite, 1-(2-pyrimidinyl)-piperazine—I. Effects of acute and long-term administration of tandospirone on serotonin neurotransmission
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It is concluded that desensitization of somatodendritic 5-HT autoreceptors permits5-HT neurones to regain their physiological rate of firing during long-term treatment with tandospirone and, consequently, to release a normal amount of 5- HT into the synaptic cleft. Expand
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