Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers

  title={Neurochemical and autonomic pharmacological profiles of the 6-aza-analogue of mianserin, org 3770 and its enantiomers},
  author={Thijs de Boer and Guido Maura and Maurizio Raiteri and Clazien J. de Vos and Johannus H. Wieringa and Roger Martin Pinder},
The neurochemical and autonomic pharmacological profile of 1,2,3,4,10, 14b-hexahydro-2-methyl-pyrazino[2,1-a]pyrido[2,3-c]pyrido[2, 3-c] [2] benzazepine [+/-)Org 3770) and the related antidepressant drug, mianserin, have been compared. The uptake of [3H]noradrenaline ([3H]NA) in vitro was weakly affected by (+/-)Org 3770 (pKi = 5.6) in contrast to mianserin (pKi = 7.4). Both (+/-)Org 3770 and mianserin facilitated the release of [3H]NA in slices of cortex. The effects of NA mediated by alpha 2… Expand
The α2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo
Abstract The antidepressant properties of Org 3770 (1,2,3,4,10,14b-hexahydro-2-methylpyrazinol[2,1-a]pyridol[2,3-c][2]benzazepine) may be mediated via blockade of auto and hetero α2-adrenoceptors.Expand
Neurochemical effects of the enantiomers of mirtazapine in normal rats.
Results of the present study suggest that in so far as alterations in these receptor populations are important for the therapeutic action of antidepressants, neither of the enantiomers appear to be more active than the racemic mixture. Expand
Investigating the Potential Role of Serotonin-2B Receptor Antagonism in the Neuronal Actions of Adjunctive Aripiprazole
5-HT2B receptor blockade rescues an SSRI-mediated decrease in DA firing activity and increases mPFC pyramidal neuron firing and bursting activity mediated by aripiprazole and in combination with escitalopram may be, at least partly, moderated by 5- HT2B receptors expressed in this brain area. Expand
Interaction between enantiomers of mianserin and ORG3770 at 5-HT3 receptors in cultured mouse neuroblastoma cells
The results indicate that the two enantiomers block the 5-HT3 receptor-mediated ion current in a mutually dependent manner. Expand
Interaction of the antidepressant mirtazapine with α2-adrenoceptors modulating the release of 5-HT in different rat brain regions in vivo
The data confirm the basic α2-adrenoceptor-blocking properties of Mir, but are only partly concordant with previous studies reporting an increase of 5-HT output after Mir alone. Expand
Interaction ORG3770 between Enantiomers of Mianserin and at 5-HT3 Receptors in Cultured Mouse Neuroblastoma Cells
Summary--Stereoselective effects of mianserin and ORG3770 on serotonin 5-HT3 receptors in mouse neuroblastoma N1E-115 cells have been investigated in radioligand binding and in whole-cell voltageExpand
Metabolism of the Newer Antidepressants
  • S. Caccia
  • Medicine
  • Clinical pharmacokinetics
  • 1998
Several chemically unrelated agents has been developed and introduced in the past decade, to supplement the earlier antidepressants, as well as drugs with distinct neurochemical profiles such as mirtazapine, nefazodone, moclobemide and tianeptine, which may explain the individual variability with all these drugs. Expand
The Selective α2-Adrenoceptor Antagonist Mirtazapine (Org 3770) Enhances Noradrenergic and 5-HT1A-Mediated Serotonergic Neurotransmission
SummaryMirtazapine (Org 3770) is a selective antagonist at α2-adrenergic auto- and heteroreceptors, which are involved in regulation of neuronal noradrenaline (norepinephrine) and serotoninExpand
Venlafaxine:a novel antidepressant compound.
Venlafaxine is a new antidepressant that inhibits the reuptake of both 5-hydroxytryptamine (serotonin; 5-HT) and noradrenaline (NA) and its efficacy is comparable to that of comparator drugs, and in some cases even greater, andIts efficacy is greater than that measured with placebo. Expand
Effects of long-term treatment with the α2-adrenoceptor antagonist mirtazapine on 5-HT neurotransmission
The tonic activation of postsynaptic 5-HT receptors is enhanced by a 21-day treatment with mirtazapine, as a result of a sustained increase in5-HT neuron firing activity in the presence of decreased function of α2-adrenergic heteroreceptors located on 5- HT terminals in the dorsal hippocampus. Expand


Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes
Results indicate that mianserin interferes in a way different from that of tricyclic antidepressants with the neurotransmitter transport mechanisms at the presynaptic level. Expand
Pharmacological characterization of presynaptic alpha-adrenoceptors modulating [3H]noradrenaline and [3H]5-hydroxytryptamine release from slices of the hippocampus of the rat.
The experiments served to characterize the receptors mediating the inhibitory effect of alpha-adrenergic drugs on K+ (20 mM)-induced [3H]noradrenaline (NA) and [ 3H]5-hydroxytryptamine ([3H)5-HT) release from slices of the dorsal part of rat hippocampus, and suggest that these alpha 2- adrenoceptors are not pharmacologically identical. Expand
Effects of antidepressant drugs on different receptors in the brain.
Radioligand receptor binding techniques were used to characterize the effects of different structural types of antidepressant drugs on neurotransmitter receptors and found that all the antidepressants tested were practically devoid of activity on DHA binding, Spiroperidol binding, [3H]flunitrazepam binding, and Naloxone binding. Expand
It is concluded that in certain situations large doses of mianserin may block noradrenaline uptake in vivo, however, in no way does mianserserin rival tricyclic antidepressants in blocking monoamine uptake in vitro and in vivo. Expand
[3H]rauwolscine (α-yohimbine): A specific antagonist radioligand for brain α2-adrenergic receptors
[3H]Rauwolscine, a specific and potent alpha 2-antagonist radioligand, was used to characterize alpha 2-receptor binding in bovine cerebral cortex. [3H]Rauwolscine binding was reversible,Expand
Dopamine receptors in human and calf brains, using [3H]apomorphine and an antipsychotic drug.
Since there was little desorption of [3H]apomorphine, the ligand permits extensive washing during routine assays for dopamine receptors, and facilitates biochemical purification of the receptor. Expand
Neuropharmacological studies in rodents on the action of RX 781094, a new selective α2-adrenoceptor antagonist
The results support the conclusion that RX 781094 is a potent antagonist at central alpha 2-adrenoceptors. Expand
Muscarinic cholinergic binding in rat brain.
  • H. Yamamura, S. Snyder
  • Chemistry, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 1974
Binding sites with high affinity and specificity for [(3)H]quinuclidinyl benzilate (QNB) are present in homogenates of rat brain. The characteristics of the binding sites resemble those of muscarinicExpand
Studies on RX 781094: a selective, potent and specific antagonist of α2‐adrenoceptors
1 The selectivity and specificity of RX 781094 [2‐(2‐(1,4 benzodioxanyl))2‐imidazoline HCl] for α‐adrenoceptors have been examined in peripheral tissues. 2 In isolated tissue experiments RX 781094Expand
α1- and α2-adrenoceptors in rat cerebral cortex: Effects of neonatal treatment with 6-hydroxydopamine
Abstract Neonatal 6-hydroxydopamine treatment was used to destroy the noradrenergic nerve terminals in rat cerebral cortex and thus give some insight into the in vivo regulation of α-adrenoceptorExpand