HP-505 explained

HP-505 is a triple reuptake inhibitor that was investigated by Hoechst-Roussel Pharmaceuticals.^[1] In mice, HP-505 was a potent inhibitor of tetrabenazine-induced ptosis which may indicate antidepressant activity.^[2]

Pharmacology

The inhibitory effect of HP-505 on serotonin reuptake is approximately 1.8 and 3.5 times stronger than on norepinephrine and dopamine, respectively. Subsequent investigations have found that HP-505 acts on presynaptic dopamine transporters and is devoid of anticholinergic effects.^[3]

Synthesis

The N-methylated analog is called HP-365 [59142-29-9].

An older synthesis is available, although more modern methods exist now:^[4]

Notes and References

1. Meyerson LR, Ong HH, Martin LL, Ellis DB . Effect of antidepressant agents on beta-adrenergic receptor and neurotransmitter regulatory systems . Pharmacology, Biochemistry, and Behavior . 12 . 6 . 943–948 . June 1980 . 6105676 . 10.1016/0091-3057(80)90457-8 . 45400599 .
2. Klioze SS, Bauer VJ, Geyer HM . Synthesis of spiro[isobenzofuran-1(3H),4'-piperidines] as potential central nervous system agents. 2. Compounds containing a heteroatom attached to nitrogen . Journal of Medicinal Chemistry . 20 . 4 . 610–612 . April 1977 . 850252 . 10.1021/jm00214a039 .
3. Book: Puri SK, Mantione CR, Petko W, Ellis DB . Spiroisobenzofuran Piperidine Derivatives. Interaction with Pre- and Post-Synaptic Dopaminergic Sites . Usdin E, Kopin IJ, Barchas J . Catecholamines: Basic and Clinical Frontiers . Pergamon . 1979 . 514–516 . 10.1016/B978-1-4832-8363-0.50158-0. 978-1-4832-8363-0 .
4. ((Maier, C. A.)), ((Wünsch, B.)) . Journal of Medicinal Chemistry . Novel Spiropiperidines as Highly Potent and Subtype Selective σ-Receptor Ligands. Part 1 . 45 . 2 . 438–448 . 1 January 2002 . 0022-2623 . 10.1021/jm010992z.