Electrophysiological, behavioural and biochemical evidence for activation of brain noradrenergic systems following neurokinin receptor stimulation

Jung, Mireille; Michaud, Jean-Claude; Steinberg, R.; Barnouin, M.C.; Hayar, Abdallah; Mons, G.; Souilhac, J.; Emonds‐Alt, Xavier; Soubrié, Philippe; Fur, G. Le

doi:10.1016/0306-4522(96)00150-9

Cited by 43 publications

(16 citation statements)

References 41 publications

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“…Previous data have suggested that direct activation of NK 3 receptors, via application of senktide either directly to cell bodies (Marco et al, 1998;Bert et al, 2002;Liu et al, 2002) or i.c.v. (Jung et al, 1996), resulted in an increase in extracellular levels of NE, DA, and 5-HT in cortical structures. It was therefore somewhat surprising that talnetant induced increases in mPFC DA and NE, and enhanced dHipp NE levels.…”

Section: Discussionmentioning

confidence: 99%

“…NK 3 receptors have also been shown to have modulatory actions on other neurotransmitter systems including NE (Jung et al, 1996;Bert et al, 2002) and 5-HT (Liu et al, 2002). Thus, talnetant was examined for its ability to modulate efflux of NE, 5-HT, and DA in the mPFC and dHipp.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, electrophysiological data have demonstrated that NK 3 receptor activation can augment NE (Jung et al, 1996) and DA cell firing (Nalivaiko et al, 1997) in the guinea pig brain. Furthermore, NK 3 receptor antagonists have been shown to attenuate dopaminergic cell firing in the guinea pig VTA and SN, induced by DA D 2 receptor and neurotensin receptor blockade (Gueudet et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

“…Neurochemical studies have shown that NK 3 receptor activation can augment dopamine (DA) and acetylcholine (ACh) efflux in the nucleus accumbens (NAcc) and caudate putamen (Marco et al, 1998), norepinephrine (NE) efflux in the mPFC (Jung et al, 1996;Bert et al, 2002) and ACh in the hippocampus (Marco et al, 1998) of the guinea pig, and g-aminobutyric acid (GABA) in the NAcc and caudate putamen of the rat (Preston et al, 2000). Similarly, electrophysiological data have demonstrated that NK 3 receptor activation can augment NE (Jung et al, 1996) and DA cell firing (Nalivaiko et al, 1997) in the guinea pig brain.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Characterization of the Non-peptide NK3 Receptor Antagonist SB-223412 (Talnetant): Potential Therapeutic Utility in the Treatment of Schizophrenia

Dawson

Cato

Scott

et al. 2007

Neuropsychopharmacol

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Neurokinin-3 (NK 3 ) receptors are concentrated in forebrain and basal ganglia structures within the mammalian CNS. This distribution, together with the modulatory influence of NK 3 receptors on monoaminergic neurotransmission, has led to the hypothesis that NK 3 receptor antagonists may have therapeutic efficacy in the treatment of psychiatric disorders. Here we describe the in vitro and in vivo characterization of the highly selective NK 3 receptor antagonist talnetant (SB-223412). Talnetant has high affinity for recombinant human NK 3 receptors (pK i 8.7) and demonstrates selectivity over other neurokinin receptors (pK i NK 2 ¼ 6.6 and NK 1 o4). In native tissuebinding studies, talnetant displayed high affinity for the guinea pig NK 3 receptor (pK i 8.5). Functionally, talnetant competitively antagonized neurokinin B (NKB)-induced responses at the human recombinant receptor in both calcium and phosphoinositol second messenger assay systems (pA 2 of 8.1 and 7.7, respectively). In guinea pig brain slices, talnetant antagonized NKB-induced increases in neuronal firing in the medial habenula (pK B ¼ 7.9) and senktide-induced increases in neuronal firing in the substantia nigra pars compacta (pK B ¼ 7.7) with no diminution of maximal agonist efficacy, suggesting competitive antagonism at native NK 3 receptors. Talnetant (3-30 mg/kg i.p.) significantly attenuated senktide-induced 'wet dog shake' behaviors in the guinea pig in a dose-dependent manner. Microdialysis studies demonstrated that acute administration of talnetant (30 mg/kg i.p.) produced significant increases in extracellular dopamine and norepinephrine in the medial prefrontal cortex and attenuated haloperidol-induced increases in nucleus accumbens dopamine levels in the freely moving guinea pigs. Taken together, these data demonstrate that talnetant is a selective, competitive, brain-penetrant NK 3 receptor antagonist with the ability to modulate mesolimbic and mesocortical dopaminergic neurotransmission and hence support its potential therapeutic utility in the treatment of schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

In Vitro and In Vivo Characterization of the Non-peptide NK3 Receptor Antagonist SB-223412 (Talnetant): Potential Therapeutic Utility in the Treatment of Schizophrenia

Dawson

Cato

Scott

et al. 2007

Neuropsychopharmacol

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“…CRF (1 g) was injected i.c.v. (free-hand method; Jung et al, 1996) 15 min (antalarmin) or 60 min (SSR125543A) later. In each experiment, a control group was injected i.c.v.…”

Section: Crf-induced Forepaw Treading In Gerbilsmentioning

confidence: 99%

4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1 S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine Hydrochloride (SSR125543A): A Potent and Selective Corticotrophin-Releasing Factor1 Receptor Antagonist. I. Biochemical and Pharmacological Characterization

Gully

Geslin²,

Serva³

et al. 2002

The Journal of Pharmacology and Experimental Therapeutics

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Will Modulation of Neuropeptide Receptors Produce the Next Generation of Antipsychotic Drugs? A Focus on the Neurokinin and Neurotensin Systems

Dawson

Smith

Watson

2012

Targets and Emerging Therapies for Schizophrenia

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Electrophysiological, behavioural and biochemical evidence for activation of brain noradrenergic systems following neurokinin receptor stimulation

Cited by 43 publications

References 41 publications

In Vitro and In Vivo Characterization of the Non-peptide NK3 Receptor Antagonist SB-223412 (Talnetant): Potential Therapeutic Utility in the Treatment of Schizophrenia

In Vitro and In Vivo Characterization of the Non-peptide NK3 Receptor Antagonist SB-223412 (Talnetant): Potential Therapeutic Utility in the Treatment of Schizophrenia

4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1 S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine Hydrochloride (SSR125543A): A Potent and Selective Corticotrophin-Releasing Factor1 Receptor Antagonist. I. Biochemical and Pharmacological Characterization

Will Modulation of Neuropeptide Receptors Produce the Next Generation of Antipsychotic Drugs? A Focus on the Neurokinin and Neurotensin Systems

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