4-Benzylpiperidine Explained

4-Benzylpiperidine is a drug and research chemical used in scientific studies. It acts as a monoamine releasing agent with 20- to 48-fold selectivity for releasing dopamine versus serotonin. It is most efficacious as a releaser of norepinephrine, with an EC₅₀ of 109 nM (DA), 41.4 nM (NE) and 5246 nM (5-HT).^[1] It has a fast onset of action and a short duration. It also functions as a monoamine oxidase inhibitor (MAOI) with preference for MAO-A.^[2]

Synthesis

4-Cyanopyridine can be reacted with toluene to give 4-benzylpyridine.^[3] Catalytic hydrogenation of the pyridine ring then completes the synthesis.^[4]

Applications

• RMI-10608 [35623-04-2] Patent (Ex 2/3):^[5] (Ex 3)^[6] This analogue of haloperidol was discovered to have utility in treating both psychosis as well as preventing brain damage by virtue of its NMDA antagonist pharmacology.

See also

• 2-Benzylpiperidine
• Benzylpiperazine
• Tetrahydroisoquinoline

Notes and References

1. Negus SS, Baumann MH, Rothman RB, Mello NK, Blough BE . Selective suppression of cocaine- versus food-maintained responding by monoamine releasers in rhesus monkeys: benzylpiperazine, (+)phenmetrazine, and 4-benzylpiperidine . The Journal of Pharmacology and Experimental Therapeutics . 329 . 1 . 272–281 . April 2009 . 19151247 . 2670586 . 10.1124/jpet.108.143701 .
2. Arai Y, Hamamichi N, Kinemuchi H . Time-dependent inhibition of rat brain monoamine oxidase by an analogue of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 4-(4-chlorophenyl)-1,2,3,6-tetrahydropyridine . Neuroscience Letters . 70 . 2 . 255–260 . October 1986 . 3490636 . 10.1016/0304-3940(86)90473-8 . 30243106 .
3. Hoshikawa T, Inoue M . Photoinduced direct 4-pyridination of C(sp3)–H Bonds . Chemical Science . 4 . 8 . 2013 . 3118 . 2041-6520 . 10.1039/c3sc51080h.
4. Book: Siegel S . Rhodium on alumina. . e-EROS Encyclopedia of Reagents for Organic Synthesis . 2001 . 1031885332 . John Wiley & Sons . New York . 10.1002/047084289X.rr003 . 978-0-471-93623-7 .
5. Rafael Foguet, et al. (1995 to Ferrer Internacional SA).
6. Sui Xiong Cai, et al. WO1996002250 (Cocensys Inc, Acea Pharmaceuticals Inc).