Effects of chronic treatment with valproate on serotonin-1A receptor binding and function

Valproate is effective in treating bipolar disorder characterized by rapid cycling or acute mania, although the mechanism of action is unclear. In contrast to other treatments for depression, 21 days of treatment in rats with valproate (100, 200 or 400 mg/kg) did not significantly alter the hypothermia induced by 8-hydroxy-2-(di-n-propyl)aminotetralin (8-OH-DPAT), an agonist at serotonin-1A receptors. Treatment with valproate also had no effect on radioligand binding to serotonin-1A, serotonin-2 or -adrenergic receptors. Based on these animal studies in frontal cortex and hippocampus, the therapeutic benefit of valproate in mood disorders does not appear to involve adaptive changes in serotonin-1A, serotonin-2 or -adrenergic receptor number.     

COMPARISON OF THE ANORECTIC AND MOTOR ACTIVITY EFFECTS OF SOME AMINOINDANES, 2-AMINOTETRALIN AND AMPHETAMINE IN THE RAT

1. The anorectic and motor activity effects of 1-aminoindane, 2-aminoindane, some N-substituted 2-aminoindanes,2-aminotetralin, amphetamine and fenfluramine were determined in rats. 2. The two compounds with structures most like the extended conformation of amphetamine, 2-aminotetralin and 2-aminoindane, were potent anorectics. At dosages which halved the intake of food over 1 h, amphetamine increased motor activity, 2-aminotetralin had no effect, and 2-aminoindane reduced motor activity.’ 3. Both the anorectic and central stimulant actions of 2-aminoindane were absent in N-ethyl- and N-isopropyl-2-aminoindane. 4. 1-Aminoindane, whose structure is like the folded conformation of amphetamine, produced a small anorectic effect and depressed motor activity.     

多巴胺D3受体配体研究现状

综述了现有多巴胺D3受体配体(主要是氨基四氢萘满类)的分子结构、受体亲和性和受体选择性进行了比较,并对多巴胺D3受体配体的研究进行了展望。     

Characterization of the dopamine D3 receptor agonist R(+)‐7‐hydroxy‐N,N‐di‐n‐propyl‐2‐aminotetralin‐induced hypo‐ and hypermotility in mice

The present study was designed to characterize the dopamine D₃ receptor agonist R(+)‐7‐hydroxy‐N,N‐di‐n‐propyl‐2‐aminotetralin (R(+)‐7‐OH‐DPAT)‐induced changes in locomotor activity in mice. Although R(+)‐7‐OH‐DPAT (0·01–10 mg/kg) produced a significant decrease in horizontal and vertical motility within 15 min after the start of behavioural measurements, the dopamine D₁ receptor antagonist R(+)‐SCH23390 (0·05 mg/kg) and the dopamine D₃ receptor antagonist (+)‐UH232 (10 mg/kg) had no antagonistic effects on the R(+)‐7‐OH‐DPAT (3 mg/kg)‐induced hypomotility, while the dopamine D₂ receptor antagonist S(−)‐sulpiride (20 mg/kg) augmented it. Although R(+)‐7‐OH‐DPAT (0·01–1 mg/kg) had no marked effects on horizontal or vertical motility, higher doses (3 and 10 mg/kg) of the drug produced a significant increase in horizontal or vertical motility from 30 to 90 min after the start of the behavioural measurements. S(−)‐sulpiride (20 mg/kg) and (+)‐UH232 (10 mg/kg) almost completely inhibited the R(+)‐7‐OH‐DPAT (3 mg/kg)‐induced hypermotility, whereas the antagonistic effects of R(+)‐SCH23390 (0·05 mg/kg) were partial. These results suggest that the R(+)‐7‐OH‐DPAT‐induced hypermotility is mediated principally via dopamine D₂ and D₃ receptors, whereas it is unlikely that the hypomotility results from the activation of presynaptic dopamine D₂ or D₃ receptors. Copyright © 1999 John Wiley & Sons, Ltd.     

Selectivity of agonists and antagonists at D2dopamine receptors compared to D1 and S2receptors

The common dopamine agonists (dopamine, apomorphine, ADTN, and N-propylnorapomorphine) are not selective D₁ or D₂ dopamine receptors, affecting both simultaneously. SK&F 38393 is selective for D₁, while bromocriptine and (D₂)D₂LYD₂171555 are selective for D₂. The neuroleptic with the highest D₂/S₂ selectivity is eticlopride with an affinity 3,200-fold higher for the D₂ dopamine receptor compared to the S₂ serotonin receptor. Such selective neuroleptics may be clinically useful and may also help in measuring the elevated D₂ density in vivo by positron emission tomography in the brains of schizophrensis.