Effects of the substituted (S)-3-phenylpiperidine (−)-OSU6162 on PET measurements in subhuman primates: Evidence for tone-dependent normalization of striatal dopaminergic activity
✍ Scribed by J. Tedroff; R. Torstenson; P. Hartvig; C. Sonesson; N. Waters; A. Carlsson; H. Neu; K.-J. Fasth; B. Långström
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 90 KB
- Volume
- 28
- Category
- Article
- ISSN
- 0887-4476
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✦ Synopsis
Ϫ)-OSU6162 is a substituted (S)-3-phenylpiperidine derivative which exhibits some affinity to the dopamine D 2 receptor family. In vivo, the compound displays a unique normalizing profile on psychomotor activity by an intriguing mixture of stimulatory and inhibitory properties. In the present investigation, some of the effects of (Ϫ)-OSU6162 on central dopaminergic function were studied by positron emission tomography (PET) and L-[ 11 C]DOPA in anaesthetized female rhesus monkeys. (Ϫ)-OSU6162 displayed a dopaminergic tone-dependent effect with a reduction in the striatal L-[ 11 C]DOPA influx rate in monkeys with high baseline values and an increased striatal L-[ 11 C]DOPA influx rate in animals with low baseline values. Infusion of (Ϫ)-OSU6162 for a whole day resulted in a stable effect with no evidence of tolerance. (Ϫ)-OSU6162 also stabilized dopaminergic function by attenuating the upregulation of the striatal L-[ 11 C]DOPA influx rate which has previously been shown to occur following 6R-BH 4 or 6R-BH 4 ϩ L-tyrosine infusions. This ''Protean'' effect of (Ϫ)-OSU6162 on the striatal dopaminergic function corresponds to previous behavioral observations in intact animals and demonstrates a true functional correlation to the measures obtained with L-[ 11 C]DOPA and PET. The normalizing and stabilizing profile of (Ϫ)-OSU6162 should be of value in treating a variety of disorders where an underlying dysregulation or disruption of dopaminergic function can be assumed.