Alkoxyfurocoumarin derivatives as potential mesolimbic selective antipsychotics

Summary A series of potential antipsychotic compounds have been synthesized by combining a furocoumarin heterocycle through a linker of different sizes with an arylpiperazine or piperidine moiety. Several of the compounds show very high affinity for the dopamine-D 1 and -D 2 , α 1 -adrenergic and serotonin 5-HT 2 receptors in vitro and selected compounds, eg, 3k, 3n and 3p , were active in in vivo models predictive of antipsychotic activity. In mice the compounds potently antagonized methylphenidate-induced motility while methylphenidate-induced gnawing was unaffected. In rats the compounds inhibited condition avoidance responding without causing catalepsy.