The selective dopamine D1 receptor agonist, SKF 81297, stimulates motor behaviour of MPTP-lesioned monkeys

Vermeulen, R. Jeroen; Drukarch, Benjamin; Sahadat, M. C. R.; Goosen, C.; Wolters, Erik Ch.; Stoof, Johannes C.

doi:10.1016/0014-2999(93)90834-5

Cited by 33 publications

(10 citation statements)

References 12 publications

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“…Furthermore, the selective dopamine D1-receptor agonist SKF 82958 with full agonistic activity as well as the dopamine D2-receptor agonist quinpirole showed the antiparkinsonian effects. These results are consistent with the previous reports that the selective dopamine D1-receptor agonists with full agonistic activity such as dihydrexidine and SKF 81297 ameliorate the parkinsonism in MPTP-lesioned monkeys (11,12). These findings together with the present results indicate that a sufficient stimulation of dopamine D1-receptors, as well as that of dopamine D2 receptors, ameliorates the symptoms of Parkinson's disease.…”

Section: Discussionsupporting

confidence: 94%

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Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

Akai¹,

Ozawa²,

Yamaguchi³

et al. 1995

Japanese Journal of Pharmacology

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ABSTRACT-To clarify the roles of dopamine D, and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D, antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D,-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D, or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D, and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.

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Section: Discussionsupporting

confidence: 94%

“…On the other hand, the another partial dopamine D,-receptor agonist CY 208-243 ameliorated the parkinsonism and potentiated the antiparkinsonian effect elicited by bromocriptine (9, 10). Recently full dopamine D,-receptor agonists such as dihydrexidine and SKF 81297 have been reported to show an antiparkinsonian effect (11,12).…”

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confidence: 99%

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

Akai¹,

Ozawa²,

Yamaguchi³

et al. 1995

Japanese Journal of Pharmacology

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“…2,3 Clinical and experimental data have implicated DA D 1 receptor subtype stimulation in the genesis of L-dopa-induced dyskinesias. Conversely, selective DA D 2 receptor stimulation is capable of inducing dyskinesias in MPTP-treated cynomolgus monkeys, 14,15 whereas antiparkinsonian activity elicited by selective DA D 1 receptor activation is clearly observed in this animal model [16][17][18][19] and in PD patients. 7 By analogy with L-dopa, this distinctive feature of bromocriptine would suggest that the DA D 2 receptor subtype is responsible for the antiparkinsonian effect, whereas dyskinesias are mediated by the DA D 1 receptor subtype.…”

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confidence: 99%

D ₁ receptor blockade improves l -dopa–induced dyskinesia but worsens parkinsonism in MPTP monkeys

et al. 1999

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Low-dose clozapine could be an effective adjunct to reduce L-dopa-induced dyskinesias without altering the relief of parkinsonian symptoms. Interactions with many neurotransmitter systems may explain the better pharmacologic profile of clozapine, including DA D4 (rather than D1), serotonin, acetylcholine, and noradrenaline. Neither dyskinesias nor antiparkinsonian effects can be ascribed solely to the D2 or D1 receptor. Thus, some cooperation between the two receptors appears necessary for these behavioral effects.

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“…1995a; Pendleton et al. 2002) and SKF81297 (Vermeulen et al. 1993), also show anti‐parkinsonian effects.…”

Section: Discussionmentioning

confidence: 99%

Regulation of DARPP‐32 phosphorylation by three distinct dopamine D₁‐like receptor signaling pathways in the neostriatum

Kuroiwa¹,

Bateup²,

Shuto³

et al. 2008

Journal of Neurochemistry

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Dopamine D1‐like receptors play a key role in dopaminergic signaling. In addition to Gs/olf/adenylyl cyclase (AC)‐coupled D1 receptors, the presence of D1‐like receptors coupled to Gq/phospholipase C (PLC) has been proposed. Benzazepine D1 receptor agonists are known to differentially activate Gs/olf/AC and Gq/PLC signaling. By utilizing SKF83959 and SKF83822, we investigated the D1‐like receptor signaling cascades, which regulate DARPP‐32 phosphorylation at Thr34 (the PKA‐site) in mouse neostriatal slices. Treatment with SKF83959 or SKF83822 increased DARPP‐32 phosphorylation. The SKF83959‐ and SKF83822‐induced increase in DARPP‐32 phosphorylation was largely, but partially, antagonized by a D1 receptor antagonist, SCH23390, and the residual SCH23390‐insensitive increase was abolished by an adenosine A2A receptor antagonist. In addition, the SKF83959‐induced, SCH23390‐sensitive increase in DARPP‐32 phosphorylation was enhanced by a PLC inhibitor. Analysis in slices from D1R/D2R‐DARPP‐32 mice revealed that both D1 receptor agonists regulate DARPP‐32 phosphorylation in striatonigral, but not in striatopallidal, neurons. Thus, dopamine D1‐like receptors are coupled to three signaling cascades in striatonigral neurons: (i) SCH23390‐sensitive Gs/olf/AC/PKA, (ii) adenosine A2A receptor‐dependent Gs/olf/AC/PKA, and (iii) Gq/PLC signaling. Interestingly, Gq/PLC signaling interacts with SCH23390‐sensitive Gs/olf/AC/PKA signaling, resulting in its inhibition. Three signaling cascades activated by D1‐like receptors likely play a distinct role in dopaminergic regulation of psychomotor functions.

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The selective dopamine D1 receptor agonist, SKF 81297, stimulates motor behaviour of MPTP-lesioned monkeys

Cited by 33 publications

References 12 publications

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

D ₁ receptor blockade improves l -dopa–induced dyskinesia but worsens parkinsonism in MPTP monkeys

Regulation of DARPP‐32 phosphorylation by three distinct dopamine D₁‐like receptor signaling pathways in the neostriatum

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The selective dopamine D1 receptor agonist, SKF 81297, stimulates motor behaviour of MPTP-lesioned monkeys

Cited by 33 publications

References 12 publications

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

Behavioral Involvement of Central Dopamine and D2 Receptors in l-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-Lesioned Parkinsonian Cynomolgus Monkeys

D 1 receptor blockade improves l -dopa–induced dyskinesia but worsens parkinsonism in MPTP monkeys

Regulation of DARPP‐32 phosphorylation by three distinct dopamine D1‐like receptor signaling pathways in the neostriatum

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D ₁ receptor blockade improves l -dopa–induced dyskinesia but worsens parkinsonism in MPTP monkeys

Regulation of DARPP‐32 phosphorylation by three distinct dopamine D₁‐like receptor signaling pathways in the neostriatum