Niaprazine

Niaprazine

Systematic (IUPAC) name
N-{4-[4-(4-fluorophenyl)piperazin- 1-yl]butan- 2-yl}pyridine- 3-carb​oxamide
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Half-life	~4.5 hours
Identifiers
CAS number	27367-90-4
ATC code	N05CM16
PubChem	CID 71919
ChemSpider	64930
UNII	R2H3YN6E3L Y
KEGG	D07333
Chemical data
Formula	C20H25FN4O
Mol. mass	356.437 g/mol
SMILES	eMolecules & PubChem

Niaprazine (Nopron) is a sedative-hypnotic drug of the phenylpiperazine class.^[1] It has been used in the treatment of sleep disturbances since the early 1970s in several European countries, including France, Italy, and Luxembourg.^[2][3] It is commonly used with children and adolescents on account of its favorable safety and tolerability profile and lack of abuse potential.^{[4][5][6][7][8][9]}

Originally believed to act as an antihistamine and anticholinergic,^[10] niaprazine was later discovered to have no significant binding affinity for either the H₁ or the mACh receptors (K_i = > 1 μM), and was instead found to act as a potent and selective 5-HT_2A and α₁-adrenergic receptor antagonist (K_i = 75 nM and 86 nM, respectively).^[11] It is virtually inactive at 5-HT_1A, 5-HT_2B, D₂, and β-adrenergic, as well as at SERT and VMAT (K_i = all > 1 μM), but it does have some weak affinity for the α₂-adrenergic receptor (K_i = 730 nM),^[11] likely acting as an antagonist there as well.

Niaprazine has been shown to metabolize to the compound pFPP in a similar manner to how trazodone and nefazodone metabolize to mCPP.^[12][13] It is unclear what role, if any, pFPP plays in the clinical effects of niaprazine.^[11] However, from animal studies it is known that pFPP, unlike niaprazine, does not produce sedative effects, and instead exerts a behavioral profile indicative of serotonergic activation.^[12]

See also

• Phenylpiperazine

References

1. ^ Kent, Angela; M. Billiard (2003). Sleep: physiology, investigations, and medicine. New York: Kluwer Academic/Plenum. ISBN 0-306-47406-9. http://books.google.com/?id=IorPrIY6dOYC&lpg=PA291&vq=niaprazine&pg=PA291#v=onepage&q. 
2. ^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN 3-88763-075-0. http://books.google.com/?id=5GpcTQD_L2oC&lpg=PA726&dq=niaprazine&pg=PA726#v=onepage&q. 
3. ^ David J. Triggle (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 0-412-46630-9. http://books.google.com/?id=A0THacd46ZsC&lpg=PA1418&dq=niaprazine&pg=PA1418#v=onepage&q. 
4. ^ Franzoni E, Masoni P, Mambelli M, Marzano P, Donati C (1987). "[Niaprazine in behavior disorders in children. Double-blind comparison with placebo]" (in Italian). La Pediatria Medica E Chirurgica : Medical and Surgical Pediatrics 9 (2): 185–7. PMID 2958783. 
5. ^ Bodiou C, Bavoux F (1988). "[Niaprazine and side effects in pediatrics. Cooperative evaluation of French centers of pharmacovigilance]" (in French). Thérapie 43 (4): 307–11. PMID 2903572. 
6. ^ Ottaviano S, Giannotti F, Cortesi F (October 1991). "The effect of niaprazine on some common sleep disorders in children. A double-blind clinical trial by means of continuous home-videorecorded sleep". Child's Nervous System : ChNS : Official Journal of the International Society for Pediatric Neurosurgery 7 (6): 332–5. PMID 1837245. 
7. ^ Montanari G, Schiaulini P, Covre A, Steffan A, Furlanut M (1992). "Niaprazine vs chlordesmethyldiazepam in sleep disturbances in pediatric outpatients". Pharmacological Research : the Official Journal of the Italian Pharmacological Society 25 Suppl 1: 83–4. PMID 1354861. 
8. ^ Younus M, Labellarte MJ (2002). "Insomnia in children: when are hypnotics indicated?". Paediatric Drugs 4 (6): 391–403. PMID 12038875. http://content.wkhealth.com/linkback/openurl?issn=1174-5878&volume=4&issue=6&spage=391. 
9. ^ Mancini J, Thirion X, Masut A, et al. (July 2006). "Anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002". Pharmacoepidemiology and Drug Safety 15 (7): 494–503. doi:10.1002/pds.1258. PMID 16700077. 
10. ^ Duchene-Marullaz P, Rispat G, Perriere JP, Hache J, Labrid C (1971). "[Some pharmacodynamical properties of niaprazine, a new antihistaminic agent]" (in French). Thérapie 26 (6): 1203–9. PMID 4401719. 
11. ^ ^{a b c} Scherman D, Hamon M, Gozlan H, et al. (1988). "Molecular pharmacology of niaprazine". Progress in Neuro-psychopharmacology & Biological Psychiatry 12 (6): 989–1001. doi:10.1016/0278-5846(88)90093-0. PMID 2853885. 
12. ^ ^{a b} Keane PE, Strolin Benedetti M, Dow J (February 1982). "The effect of niaprazine on the turnover of 5-hydroxytryptamine in the rat brain". Neuropharmacology 21 (2): 163–9. doi:10.1016/0028-3908(82)90157-5. PMID 6460945. 
13. ^ International review of neurobiology. New York: Academic Press. 1988. ISBN 0-12-366829-8. http://books.google.com/?id=Uf_BWXKXW2cC&lpg=PA274&dq=niaprazine&pg=PA274#v=onepage&q.