PMID- 10611634
OWN - NLM
STAT- MEDLINE
DCOM- 20000217
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 35
IP  - 2
DP  - 2000 Feb
TI  - Agonist and antagonist actions of yohimbine as compared to fluparoxan at 
      alpha(2)-adrenergic receptors (AR)s, serotonin (5-HT)(1A), 5-HT(1B), 5-HT(1D) and 
      dopamine D(2) and D(3) receptors. Significance for the modulation of 
      frontocortical monoaminergic transmission and depressive states.
PG  - 79-95
AB  - Herein, we evaluate the interaction of the alpha(2)-AR antagonist, yohimbine, as 
      compared to fluparoxan, at multiple monoaminergic receptors and examine their 
      roles in the modulation of adrenergic, dopaminergic and serotonergic transmission 
      in freely-moving rats. Yohimbine displays marked affinity at human (h)alpha(2A)-, 
      halpha(2B)- and halpha(2C)-ARs, significant affinity for h5-HT(1A), h5-HT(1B), 
      h5-HT(1D), and hD(2) receptors and weak affinity for hD(3) receptors. In 
      [(35)S]GTPgammaS binding protocols, yohimbine exerts antagonist actions at 
      halpha(2A)-AR, h5-HT(1B), h5-HT(1D), and hD(2) sites, yet partial agonist actions 
      at h5-HT(1A) sites. In vivo, agonist actions of yohimbine at 5-HT(1A) sites are 
      revealed by WAY100,635-reversible induction of hypothermia in the rat. In guinea 
      pigs, antagonist actions of yohimbine at 5-HT(1B) receptors are revealed by 
      blockade of hypothermia evoked by the 5-HT(1B) agonist, GR46,611. In distinction 
      to yohimbine, fluparoxan shows only modest partial agonist actions at h5-HT(1A) 
      sites versus marked antagonist actions at halpha(2)-ARs. While fluparoxan 
      selectively enhances hippocampal noradrenaline (NAD) turnover, yohimbine also 
      enhances striatal dopamine (DA) turnover and suppresses striatal turnover of 
      5-HT. Further, yohimbine decreases firing of serotonergic neurones in raphe 
      nuclei, an action reversed by WAY100,635. Fluparoxan increases extracellular 
      levels of DA and NAD, but not 5-HT, in frontal cortex. In analogy, yohimbine 
      enhances FCX levels of DA and NAD, yet suppresses those of 5-HT, the latter 
      effect being antagonized by WAY100,635. The induction by fluoxetine of FCX levels 
      of 5-HT, DA, and NAD is potentiated by fluparoxan. Yohimbine likewise facilitates 
      the influence of fluoxetine upon DA and NAD levels, but not those of 5-HT. In 
      conclusion, the alpha(2)-AR antagonist properties of yohimbine increase DA and 
      NAD levels both alone and in association with fluoxetine. However, in contrast to 
      the selective alpha(2)-AR antagonist, fluparoxan, the 5-HT(1A) agonist actions of 
      yohimbine suppress 5-HT levels alone and underlie its inability to augment the 
      influence of fluoxetine upon 5-HT levels.
CI  - Copyright 2000 Wiley-Liss, Inc.
FAU - Millan, M J
AU  - Millan MJ
AD  - Psychopharmacology Department, Institut de Recherches Servier, Centre de 
      Recherches de Croissy, 125, Chemin de Ronde, 78290-Croissy-sur-Seine, Paris, 
      France.
FAU - Newman-Tancredi, A
AU  - Newman-Tancredi A
FAU - Audinot, V
AU  - Audinot V
FAU - Cussac, D
AU  - Cussac D
FAU - Lejeune, F
AU  - Lejeune F
FAU - Nicolas, J P
AU  - Nicolas JP
FAU - Coge, F
AU  - Coge F
FAU - Galizzi, J P
AU  - Galizzi JP
FAU - Boutin, J A
AU  - Boutin JA
FAU - Rivet, J M
AU  - Rivet JM
FAU - Dekeyne, A
AU  - Dekeyne A
FAU - Gobert, A
AU  - Gobert A
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Adrenergic alpha-2 Receptor Agonists)
RN  - 0 (Adrenergic alpha-2 Receptor Antagonists)
RN  - 0 (Adrenergic alpha-Antagonists)
RN  - 0 (Antidepressive Agents)
RN  - 0 (DRD3 protein, human)
RN  - 0 (Drd3 protein, mouse)
RN  - 0 (Drd3 protein, rat)
RN  - 0 (HTR1B protein, human)
RN  - 0 (Pyrroles)
RN  - 0 (Receptor, Serotonin, 5-HT1B)
RN  - 0 (Receptor, Serotonin, 5-HT1D)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, Dopamine D3)
RN  - 0 (Receptors, Serotonin)
RN  - 0 (Receptors, Serotonin, 5-HT1)
RN  - 2Y49VWD90Q (Yohimbine)
RN  - 9ZCS27634Y (Piperoxan)
RN  - WGA8E072GX (fluparoxan)
SB  - IM
MH  - *Adrenergic alpha-2 Receptor Agonists
MH  - Adrenergic alpha-2 Receptor Antagonists
MH  - Adrenergic alpha-Antagonists/pharmacology
MH  - Animals
MH  - Antidepressive Agents/pharmacology
MH  - Body Temperature/drug effects
MH  - Frontal Lobe/drug effects/*physiology
MH  - Guinea Pigs
MH  - Hippocampus/drug effects/physiology
MH  - Humans
MH  - Mice
MH  - Neurons/drug effects/physiology
MH  - Piperoxan/*analogs & derivatives/pharmacology
MH  - Pyrroles/*pharmacology
MH  - Rats
MH  - Receptor, Serotonin, 5-HT1B
MH  - Receptor, Serotonin, 5-HT1D
MH  - Receptors, Dopamine D2/drug effects/*physiology
MH  - Receptors, Dopamine D3
MH  - Receptors, Serotonin/drug effects/*physiology
MH  - Receptors, Serotonin, 5-HT1
MH  - Swine
MH  - Synaptic Transmission/drug effects/*physiology
MH  - Yohimbine/*pharmacology
EDAT- 1999/12/28 09:00
MHDA- 2000/02/19 09:00
CRDT- 1999/12/28 09:00
PHST- 1999/12/28 09:00 [pubmed]
PHST- 2000/02/19 09:00 [medline]
PHST- 1999/12/28 09:00 [entrez]
AID - 10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X [pii]
AID - 10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X [doi]
PST - ppublish
SO  - Synapse. 2000 Feb;35(2):79-95. doi: 
      10.1002/(SICI)1098-2396(200002)35:2<79::AID-SYN1>3.0.CO;2-X.