3-PPP explained

3-PPP (N-n-propyl-3-(3-hydroxyphenyl)piperidine) is a mixed sigma σ1 and σ2 receptor agonist (with similar affinity for both subtypes, though slightly higher affinity for the latter)[1] and D2 receptor partial agonist which is used in scientific research.[2] [3] It shows stereoselectivity in its pharmacodynamics. (+)-3-PPP is the enantiomer that acts as an agonist of the sigma receptors; it is also an agonist of both D2 presynaptic and postsynaptic receptors. Conversely, (−)-3-PPP, also known as preclamol, acts as an agonist of presynaptic D2 receptors but as an antagonist of postsynaptic D2 receptors, and has antipsychotic effects.[4] 3-PPP has also been reported to be a monoamine reuptake inhibitor and possibly to act at adrenergic receptors or some other non-sigma receptor.[5]

Synthesis

The Grignard reagent was prepared for 3-Bromoanisole [2398-37-0] (1) and this was reacted with 3-Bromopyridine [626-55-1] (2) to give 3-(3-methoxyphenyl)pyridine [4373-67-5] (3). Reaction with 1-bromopropane [106-94-5] occurred to give the quaternary salt PC13695099 (4a). Catalytic hydrogenation of the quat cation gave 3-(3-methoxyphenyl)-1-propylpiperidine [86562-23-4] (5). Demethylation with hydrogen bromide then completed the synthesis of preclamol (6).

See also

Notes and References

  1. Hellewell SB, Bowen WD . A sigma-like binding site in rat pheochromocytoma (PC12) cells: decreased affinity for (+)-benzomorphans and lower molecular weight suggest a different sigma receptor form from that of guinea pig brain . Brain Res. . 527 . 2 . 244–253 . 1990 . 2174717 . 10.1016/0006-8993(90)91143-5. 24546226 .
  2. Hjorth S, Carlsson A, Clark D, Svensson K, Wikström H, Sanchez D, Lindberg P, Hacksell U, Arvidsson LE, Johansson A . Central dopamine receptor agonist and antagonist actions of the enantiomers of 3-PPP . Psychopharmacology . 81 . 2 . 89–99 . 1983 . 6415751 . 10.1007/bf00428999. 1168359 .
  3. Hellewell SB, Bruce A, Feinstein G, Orringer J, Williams W, Bowen WD . Rat liver and kidney contain high densities of sigma 1 and sigma 2 receptors: characterization by ligand binding and photoaffinity labeling . Eur. J. Pharmacol. . 268 . 1 . 9–18 . 1994 . 7925616 . 10.1016/0922-4106(94)90115-5.
  4. Book: Jeffrey S. Albert. Targets and Emerging Therapies for Schizophrenia. 6 June 2012. John Wiley & Sons. 978-1-118-30940-7. 64–.
  5. Book: Annual Reports in Medicinal Chemistry. 5 October 1993. Academic Press. 978-0-08-058372-3. 14–.