The dopamine autoreceptor agonist B-HT 920 stimulates denervated postsynaptic brain dopamine receptors in rodent and primate models of Parkinson's disease: a novel approach to treatment

Hinzen, Dieter; Hornykiewicz, Oleh; Kobinger, W.; Pichler, Ludwig; Pifl, Christian; Schingnitz, G.

doi:10.1016/0014-2999(86)90517-0

Cited by 99 publications

(28 citation statements)

References 30 publications

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“…Since DA neurones are degenerated in this condition, the effect of agonists in 6-OHDA-lesioned rats may be used for evaluation of the potential in treatment of parkinsonism. It should be noted, however, that in another model for parkinsonism, the MPTPtreated monkey, B-HT 920 and terguride are effective, whereas (--)-3-PPP has no effect (Hinzen et al, 1986;Nomoto et al, 1986;Br/icke et al, 1988). The reason for the discrepancy between rat and monkey studies is unknown, but rank order of agonist efficacies apparently differ between the two species.…”

Section: Discussionmentioning

confidence: 94%

Dopamine D-2 agonists with high and low efficacies: differentiation by behavioural techniques

Arnt

Hyttel

1990

J. Neural Transmission

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The effects of the dopamine (DA) D-2 antagonist YM 09151-2 and the DA D-2 agonists terguride, preclamol, EMD 23448, B-HT 920, quinpirole and (-)-NPA were studied in a battery of behavioural tests in order to evaluate their relative efficacies. Furthermore, their affinities for DA D-2 receptors labelled by 3H-N-0437 were measured in vitro. All agonists reduced spontaneous locomotor activity and induced marked contralateral circling behaviour in 6-hydroxy-DA-lesioned rats. Quinpirole and (-)-NPA increased motor activity after high doses. YM 09151-2 did not induce circling. In hemitransected rats quinpirole and (-)-NPA had weak effects when given alone, whereas the other agonists were ineffective. After combination with DA D-1 agonist SK&F 38393, B-HT 920 became effective, and the effects of quinpirole and (-)-NPA were facilitated. EMD 23448, preclamol and terguride were not active. In contrast, the two latter compounds fully inhibited the response to apomorphine. In stereotypy experiments a similar activity pattern was observed. Finally, drug discrimination studies showed that quinpirole, (-)-NPA and B-HT 920 substituted for the stimulus effects induced by d-amphetamine or (-)-NPA in different groups of rats. EMD 23448 induced intermediate effects, whereas preclamol and terguride had weak effects. None of the partial agonists inhibited the response of d-amphetamine. YM 09151-2 potently inhibited the effect of d-amphetamine. The results suggest that DA D-2 agonists can be ranked according to gradually increasing agonist efficacies rather than classified into autoreceptor-selective versus nonselective D-2 agonists. Implications of this hypothesis are discussed.

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Section: Discussionmentioning

confidence: 94%

Dopamine D-2 agonists with high and low efficacies: differentiation by behavioural techniques

Arnt

Hyttel

1990

J. Neural Transmission

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“…B-HT 920 has been proposed not to exert postsynaptic dopaminergic effects such as locomotor hyperactivity and stereotyped behavior in naive animals with normosensitive brain dopamine receptors (And6n et al, 1983;Hinzen et al, 1986). However, more recent observations show that B-HT 920 can exhibit postsynaptic dopamine receptor agonistic properties after co-treatment with a dopamine Dl-receptor agonist, SK&F 38393 (Hjorth and Carlsson, 1987;Pifl and Hornykiewicz, 1988;Meltzer et al, 1988).…”

Section: Discussionmentioning

confidence: 95%

Potentiation of yawning responses to the dopamine receptor agonists B-HT 920 and SND 919 by pindolol in the rat

Yamada

Matsumoto

Nagashima

et al. 1990

J. Neural Transmission

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Subcutaneous injection of B-HT 920, a dopamine D2-receptor agonist, in doses ranging from 5 to 100 micrograms/kg, induced yawning behavior in rats. Yawning was also elicited by low doses (25-500 micrograms/kg sc) of SND 919, a newly synthesized dopamine receptor agonist. The yawning evoked by B-HT 920 or SND 919 was increased by the beta-adrenoceptor antagonist pindolol (20 mg/kg ip) which alone did not induce yawning. Stereotyped behavior did not appear after B-HT 920 or SND 919 given alone or in combination with pindolol. The results suggest that SND 919 as well as B-HT 920 has stimulatory activity at dopamine D2-receptors, and that pindolol may exert its enhancement of the yawning response to dopamine receptor agonists via blockade of beta-adrenoceptors.

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“…Its protective dose, 1 mg/kg, was higher than those improving parkinsonian symptoms in con trolled clinical trials (maximum daily dose was set at 3.6 or 4.8 mg/day) (28,29), in MPTP-treated monkeys (0.01-0.2 mg/kg) (15,30), or in cynomolgus monkeys with unilateral lesion in the ventromedial tegmentum (0.025-0.2 mg/kg) (31). The clinical significance of the neuroprotective effects of talipexole should be further examined by employing lower doses.…”

Section: Discussionmentioning

confidence: 99%

“…Both talipexole and pramipexole are azepine-deriva tives that are D2-receptor agonists lacking the ability of D1-receptor stimulation, and they showed similar effects on [3H]spiperone binding (12) or MPTP-induced parkin sonian symptoms (15,16). Therefore, further studies were performed with talipexole.…”

Section: Discussionmentioning

confidence: 99%

Inhibitory Effects of Talipexole and Pramipexole on MPTP-Induced Dopamine Reduction in the Striatum of C57BL/6N Mice.

et al. 1997

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ABSTRACT-Wehave investigated the effects of two novel antiparkinsonian drugs, talipexole (Domin®) and pramipexole, on MPTP-induced dopamine (DA) reduction in the striatum of C57BL/6N mice in comparison with those of bromocriptine. Fifteen days after MPTP treatment (25 mg/kg, i.p., given daily for 5 days), the DA content in the striatum was decreased to 40-60010 of the control value. Among the three dopamine receptor agonists, talipexole and pramipexole (1 mg/kg, i.p., once a day for 20 days) more sig nificantly suppressed the MPTP-induced DA reduction in the striatum than bromocriptine (10 mg/kg, i.p., once a day for 20 days). Talipexole did not influence [3H]MPP+ uptake into striatal synaptosomes. These results suggest that talipexole and pramipexole have a protective effect against MPTP-induced DA reduc tion in the striatum of C57BL/6N mice.

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The dopamine autoreceptor agonist B-HT 920 stimulates denervated postsynaptic brain dopamine receptors in rodent and primate models of Parkinson's disease: a novel approach to treatment

Cited by 99 publications

References 30 publications

Dopamine D-2 agonists with high and low efficacies: differentiation by behavioural techniques

Dopamine D-2 agonists with high and low efficacies: differentiation by behavioural techniques

Potentiation of yawning responses to the dopamine receptor agonists B-HT 920 and SND 919 by pindolol in the rat

Inhibitory Effects of Talipexole and Pramipexole on MPTP-Induced Dopamine Reduction in the Striatum of C57BL/6N Mice.

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