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5HT-receptor antagonist properties of SCH 23390 in vascular smooth muscle and brain

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Abstract

The dopamine D1-receptor antagonist SCH 23390 was a potent competitive antagonist of 5HT-induced vasoconstriction in the isolated perfused rat tail artery preparation (pA2 8.17) but a very weak antagonist of phenylephrine-induced responses (pA2 5.94). In rat brain cerebral cortex, SCH 23390 inhibited 5-HT2-sensitive [3H]spiperone binding with an IC50 of 112 nM. Binding of [3H]5HT to 5HT1 receptors in the cortex was inhibited by SCH 23390 with an IC50 of 2.49 μM. SCH 23390 has significant affinity for 5HT receptors in addition to the reported selective dopamine D1-receptor antagonist properties.

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Cited by (94)

  • Microinjections of a dopamine D1 receptor antagonist into the ventral tegmental area block the expression of cocaine conditioned place preference in rats

    2014, Behavioural Brain Research
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    Therefore, it is possible that intra-VTA microinjections of SCH 23390 reduced the expression of cocaine CPP by reducing DA cell activity and release through blockade of DA somatic D5 receptors. SCH 23390 also can act as an agonist at 5-HT2c receptors [93–97]. Thus, the observed results of intra-VTA injections of SCH 23390 on cocaine CPP might be due to 5-HT2c receptor agonist action.

  • Involvement of adenosine A<inf>2A</inf> and dopamine receptors in the locomotor and sensitizing effects of cocaine

    2006, Brain Research
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    This result differs from the previous finding of White et al. (1998) who have shown that SCH 23390 reduced the expression of cocaine sensitization, but a higher dose of SCH 23390 (0.5 mg/kg) was used in that experiment. It should be added that SCH 23390, apart from its affinity for DA D1R resulting in D1 antagonistic activity (Borsini et al., 1995; Hall et al., 1986), displays in in vitro functional assays either agonistic (Briggs et al., 1991) or antagonistic (Hicks et al., 1984; Hoyer et al., 1989) activity at 5-HT2 receptors which suggests also the contribution of these receptors in the action of SCH 23390. Since 5-HT2 receptors have a role in controlling expression of cocaine sensitization (Filip et al., 2004), the question arises if actions at 5-HT2 receptors were responsible for the effect of the higher dose of SCH 23390 used in the experiment by White et al. (1998).

  • Prefrontal cortex D1 modulation of the reinforcing properties of cocaine

    2006, Brain Research
    Citation Excerpt :

    Differences in intra-PFC SCH 23390 dosing may account for this discrepancy as the concentrations (0.5–2.0 μg/side) were 2- to 8-fold greater than in the present study. It is notable that, in addition to binding to D1 receptors, SCH 23390 has been demonstrated to have a weak affinity for 5-HT1, 5-HT2 and α-adrenergic receptors (Bischoff et al., 1986, 1988; Hicks et al., 1984). Therefore, high doses of SCH 23390 increase both the impact on D1 receptors and the likelihood of immediate interactions with additional receptors.

  • Somatodendritic dopamine release in rat substantia nigra influences motor performance on the accelerating rod

    2003, Brain Research
    Citation Excerpt :

    A previous study by Timmerman and Abercrombie [46] reported that increases in motor activity evoked by nigral amphetamine injections could be blocked by co-injections of SCH 23390, indicating that D1/D5-receptors in SN can have a facilitating role for motor activity. In the literature, SCH 23390 concentrations of 1–100 μM are often used for reverse dialysis, and the results are interpreted as D1/D5-specific, but even though only a small fraction of the perfused substance reaches the tissue, the selectivity for D1/D5- over D2/D3-receptors can be questioned with this regime (see Ref. [26]) and SCH 23390 may, at 100 μM, even affect 5HT-receptors or potassium channels [20,28]. We can therefore not exclude that some motor impairment seen with 10 and 100 μM SCH 23390 is non-specific.

  • Intra-prefrontal cortex injections of SCH 23390 influence nucleus accumbens dopamine levels 24 h post-infusion

    2001, Brain Research
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    Another potential explanation for finding that intra-mPFC D1 antagonist, but not the agonist, influenced NAcc DA levels is the possible binding of SCH 23390 with other receptors. In addition to binding to dopamine D1 receptors, SCH 23390 has been demonstrated to have a weak affinity for 5-HT1, 5-HT2 and α-adrenergic receptors [6,7,26]. One study suggests that intra-mPFC SCH 23390 exerts effects on the mesolimbic DA system independent of actions on 5-HT or adrenergic receptors.

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