Alkoxyfurocoumarin derivatives as potential mesolimbic selective antipsychotics

• Published in: European journal of medicinal chemistry Vol. 32; no. 2; pp. 103 - 111
• Main Authors: Bondo Hansen, J, Fink-Jensen, A, Hansen, L, Nielsen, EB, Scheideler, MA
• Format: Journal Article
• Language: English
• Published: ISSY-LES-MOULINEAUX Elsevier Masson SAS 1997; Elsevier
• Subjects: adrenergic activity; alkoxyfurocoumarine; antipsychotic activity; Biological and medical sciences; Chemistry, Medicinal; dopamine; Life Sciences & Biomedicine; Medical sciences; mesolimbic selectivity; Neuropharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; receptor binding; Science & Technology; serotonin; serotonin; alkoxyfurocoumarine; adrenergic activity; antipsychotic activity; receptor binding; dopamine; mesolimbic selectivity; CLOZAPINE; ANTAGONIST; RAT; HALOPERIDOL; SCHIZOPHRENIA; DOPAMINE NEURONS; NEUROLEPTICS; AGENTS; RECEPTORS; EXPRESSION; Rat; Ligand; Neuroleptic; Psychotropic; Central nervous system; Oxygen heterocycle; Structure activity relation; Piperidine derivatives; Antipsychotic; Aromatic compound; Chemical synthesis; Dopamine receptor; Rodentia; 5-HT2 receptor; Aminoether; Lactone; Tricyclic compound; In vitro; In vivo; Vertebrata; Biological fixation; Mammalia; Mouse; Animal; Affinity; Adrenergic receptor; Brain (vertebrata)
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(97)87536-8

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.