Differential inverse agonist efficacies of SB-258719, SB-258741 and SB-269970 at human recombinant serotonin 5-HT7 receptors

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

“…The 5-HT 7 receptor is a potential target of relevance to schizophrenia as many atypical antipsychotics such as risperidone and ziprasidone have affinity for this receptor (Roth et al, 1994;Siegfried et al, 2005), and some e.g. clozapine have significant inverse agonist activity (Mahe et al, 2004). The results of experiment 1 with SB-269970A showed that 3.0 and 10.0 mg/kg of SB-269970A significantly ameliorated the PCP-induced deficit.…”

Potentiation of Morphine Analgesia by Adjuvant Activation of 5-HT7 Receptors

“…The antinociceptive effect of morphine administered either systemically or into the rostroventromedial medulla was blocked by intrathecal administration of the selective 5-HT 7 receptor antagonist SB-269970 (1,2). Similarly, intrathecal injection of the 5-HT 7 receptor antagonists SB-269970 and SB-258719 has been recently shown to block the antinociceptive and antihyperalgesic effects of both tramadol and its opioid metabolite M1 (3).…”

“…Available data in the literature suggest that spinal activation of 5-HT 7 receptors is ultimately critical in the expression of opiate-induced analgesia, likely through activation of descending inhibition. The antinociceptive effect of morphine administered either systemically or into the rostroventromedial medulla was blocked by intrathecal administration of the selective 5-HT 7 receptor antagonist SB-269970 (1,2).…”

“…Because selective 5-HT 7 receptor antagonists reversed the antinociceptive effects of morphine, it can be hypothesized that activation of 5-HT 7 receptors might enhance morphine-induced antinociception. To test this hypothesis, we evaluated the analgesic effect of morphine co-administered with the selective 5-HT 7 receptor agonist E-55888, the antagonist SB-258719, or both.…”

“…E-55888 is a potent selective 5-HT 7 receptor agonist whose affinity, functionality and selectivity profile has been previously described (5), and SB-258719 is a potent selective 5-HT 7 receptor antagonist used as a pharmacological tool (6,7).…”