Niaprazine

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Niaprazine
Niaprazine.svg
Systematic (IUPAC) name
N-{4-[4-(4-fluorophenyl)piperazin- 1-yl]butan- 2-yl}pyridine- 3-carboxamide
Clinical data
AHFS/Drugs.com International Drug Names
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 YesY
KEGG D07333
Chemical data
Formula C20H25FN4O 
Mol. mass 356.437 g/mol

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 (Ki = > 1 μM), and was instead found to act as a potent and selective 5-HT2A and α1-adrenergic receptor antagonist (Ki = 75 nM and 86 nM, respectively).[11] It is virtually inactive at 5-HT1A, 5-HT2B, D2, and β-adrenergic, as well as at SERT and VMAT (Ki = all > 1 μM), but it does have some weak affinity for the α2-adrenergic receptor (Ki = 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[edit]

References[edit]

  1. ^ Kent, Angela; M. Billiard (2003). Sleep: physiology, investigations, and medicine. New York: Kluwer Academic/Plenum. ISBN 0-306-47406-9. 
  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. 
  3. ^ David J. Triggle (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 0-412-46630-9. 
  4. ^ Franzoni E, Masoni P, Mambelli M, Marzano P, Donati C (1987). "[Niaprazine in behavior disorders in children. Double-blind comparison with placebo]". La Pediatria Medica E Chirurgica : Medical and Surgical Pediatrics (in Italian) 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]". Thérapie (in French) 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. doi:10.1007/bf00304832. 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. doi:10.1016/1043-6618(92)90551-l. PMID 1354861. 
  8. ^ Younus M, Labellarte MJ (2002). "Insomnia in children: when are hypnotics indicated?". Paediatric Drugs 4 (6): 391–403. doi:10.2165/00128072-200204060-00006. PMID 12038875. 
  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]". Thérapie (in French) 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.