Comparison of [3H]YM-09151-2 with [3H]spiperone and [3H]raclopride for dopamine D-2 receptor binding to rat striatum

Terai, Michio; Hidaka, Kazuyuki; Nakamura, Yukie

doi:10.1016/0014-2999(89)90516-5

Cited by 125 publications

(46 citation statements)

References 11 publications

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“…Nemonapride has a high affinity and selectivity for D 2 like receptors (Terai et al 1989); however, this drug is not selective for either D 3 or D 4 receptors over D 2 receptors . In contrast, YM-43611 exhibits moderate selectivity for D 3 receptors and high selectivity for D 4 receptors.…”

Section: Discussionmentioning

confidence: 99%

Effects of YM-43611, a Novel Dopamine D2-Like Receptor Antagonist, on Immediate Early Gene Expression in the Rat Forebrain

Kurokawa

Narita

Koshiya³

et al. 1997

Neuropsychopharmacology

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The pharmacological characteristics of two benzamides, YM-43611, a potent and selective dopamine D 3 and D 4 antagonist, and YM-09151-2 (nemonapride), were compared with two reference antipsychotic agents, haloperidol and clozapine, in terms of modification of c-fos and related gene expression in the rat forebrain. After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg), haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was employed, and the distributions of Fos-like immunoreactive neurons were compared. As was the case for the two reference antipsychotics, the two benzamides enhanced c-Fos immunoreactivity in a number of forebrain regions. Specifically, like clozapine and nemonapride, YM-43611 significantly increased the number of immunoreactive cells in the nucleus accumbens shell and islands of Calleja. In contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression in the medial prefrontal cortex. Haloperidol and nemonapride elevated the number of positive cells in the striatum and nucleus accumbens core, whereas clozapine and YM-43611 did not. Clozapine increased the number of Fos-like immunoreactive cells in the lateral septal nucleus and the diagonal band nucleusThe mechanism by which neuroleptics induce therapeutic effects remains elusive. Early receptor binding studies demonstrated a strong correlation between clinical potency and antagonism of the classical dopamine D 2 receptor (Creese et al. 1976;Seeman et al. 1976). Although recent pharmacological successes have implicated the potential role of several of the newly discovered dopamine receptors (D 3 , D 4 , D 5 ), nondopamine receptors, including serotonergic, adrenergic, and cholinergic receptors, are believed to subserve a specialized function in both the therapeutic action and side effect profiles of antipsychotic drugs (Deutch et al. 1991).Immediate early genes (IEGs), such as c-fos , can be activated by a variety of physiological and pharmacological stimuli and mediate the synthesis of phosphoprotein Fos Herschman 1989 Presented at the 35th annual meeting of A.C.N.P., San Juan, December 1996.Received July 29, 1996; revised December 17, 1996; accepted December 18, 1996. 28 K. Kurokawa et al. N EUROPSYCHOPHARMACOLOGY 1997 -VOL . 17 , NO . 1 that haloperidol, a typical neuroleptic, and clozapine, an atypical antipsychotic, significantly increase neuronal c-fos and related gene expression in a number of forebrain regions (Dragunow et al. 1990;Deutch et al. 1992;Nguyen et al. 1992; Robertson and Fibiger 1992;MacGibbon et al. 1994;Fink-Jensen et al. 1995;Wan et al. 1995). These studies have indicated that typical and atypical antipsychotic drugs exert regionally distinct effects on neuronal IEG expression in the striatum, lateral septum, and islands of Calleja, although they exhibit quite similar actions on c-fos expression in the nucleus accumbens shell.In addition to remoxipride, two benzamide derivatives have been introduced as selective antagonists for the dopamine D 2 -l...

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Section: Discussionmentioning

confidence: 99%

Effects of YM-43611, a Novel Dopamine D2-Like Receptor Antagonist, on Immediate Early Gene Expression in the Rat Forebrain

Kurokawa

Narita

Koshiya³

et al. 1997

Neuropsychopharmacology

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“…YM-43611 shifted the inhibition curve of dopamine on hD3 receptor-mediated cyclic AMP formation to the right; maximal inhibition was not affected by 100 nM YM-43611 (Figure 3). To assess more stringently the antagonistic properties of YM-43611 on hD2 and hD4 receptors, we performed Schild analyses using several YM-43611 concentrations (Figure 4) (Iwanami et al, 1981;Terai et al, 1989). In our studies on a series of benzamide derivatives, we found that varying 4-substituents on the benzamide could affect affinity and selectivity for the D2-like receptor subtypes (data not shown).…”

Section: Discussionmentioning

confidence: 99%

“…We previously developed a benzamide, nemonapride (YM-09151-2; Figure 1), which showed the pharmacological profile of a neuroleptic in in vivo studies (Iwanami et al, 1981;Usuda et al, 1981). Nemonapride has selectivity and potent affinity for D2-like receptors (Terai et al, 1989); in common with other neuroleptics, it is not selective for either D3 or D4 receptors over D2 receptors. In the search for a novel class of D2-like receptor ligands, we found ( Figure 1 Pharmacology (1996) 117,[1625][1626][1627][1628][1629][1630][1631][1632] Methods…”

Section: Introductionmentioning

confidence: 99%

In vitro pharmacological profile of YM‐43611, a novel D₂‐like receptor antagonist with high affinity and selectivity for dopamine D₃ and D₄ receptors

Hidaka¹,

Tada²,

Matsumoto³

et al. 1996

British J Pharmacology

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“…Washed membranes were prepared from brain regions and were incubated with tritiated ligands as described (23)(24)(25)(26)(27)(28)(29)(30). Reactions were terminated by the addition of ice-cold buffered solutions as described (23)(24)(25)(26)(27)(28)(29)(30), and membrane-associated ligand estimated after rapid filtration over Whatman GF͞B filters using a Brandel apparatus. VMAT2, serotonin transporter, norepinephrine transporter, dopamine transporter, dopamine D 1 and D 2 receptor, serotonin 5HT 1 Measurement of Blood Pressure and Heart Rates.…”

Section: Methodsmentioning

confidence: 99%

VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity

Takahashi

Miner

Sora

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

379

312

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The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP ؉ ) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP ؉ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP ؉ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion.

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Comparison of [3H]YM-09151-2 with [3H]spiperone and [3H]raclopride for dopamine D-2 receptor binding to rat striatum

Cited by 125 publications

References 11 publications

Effects of YM-43611, a Novel Dopamine D2-Like Receptor Antagonist, on Immediate Early Gene Expression in the Rat Forebrain

Effects of YM-43611, a Novel Dopamine D2-Like Receptor Antagonist, on Immediate Early Gene Expression in the Rat Forebrain

In vitro pharmacological profile of YM‐43611, a novel D₂‐like receptor antagonist with high affinity and selectivity for dopamine D₃ and D₄ receptors

VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity

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Comparison of [3H]YM-09151-2 with [3H]spiperone and [3H]raclopride for dopamine D-2 receptor binding to rat striatum

Cited by 125 publications

References 11 publications

Effects of YM-43611, a Novel Dopamine D2-Like Receptor Antagonist, on Immediate Early Gene Expression in the Rat Forebrain

Effects of YM-43611, a Novel Dopamine D2-Like Receptor Antagonist, on Immediate Early Gene Expression in the Rat Forebrain

In vitro pharmacological profile of YM‐43611, a novel D2‐like receptor antagonist with high affinity and selectivity for dopamine D3 and D4 receptors

VMAT2 knockout mice: Heterozygotes display reduced amphetamine-conditioned reward, enhanced amphetamine locomotion, and enhanced MPTP toxicity

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In vitro pharmacological profile of YM‐43611, a novel D₂‐like receptor antagonist with high affinity and selectivity for dopamine D₃ and D₄ receptors