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Niaprazine

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Niaprazine
Clinical data
Trade namesNopron
Other namesCERM-1709
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokineticdata
Eliminationhalf-life~4.5 hours
Identifiers
  • N-{4-[4-(4-fluorophenyl)piperazin- 1-yl]butan- 2-yl}pyridine- 3-carboxamide
CAS Number
PubChemCID
ChemSpider
UNII
KEGG
CompTox Dashboard(EPA)
ECHA InfoCard100.044.014Edit this at Wikidata
Chemical and physical data
FormulaC20H25FN4O
Molar mass356.445g·mol−1
3D model (JSmol)
  • Fc3ccc(N2CCN(CCC(NC(=O)c1cccnc1)C)CC2)cc3
  • InChI=1S/C20H25FN4O/c1-16(23-20(26)17-3-2-9-22-15-17)8-10-24-11-13-25(14-12-24)19-6-4-18(21)5-7-19/h2-7,9,15-16H,8,10-14H2,1H3,(H,23,26)
  • Key:RSKQGBFMNPDPLR-UHFFFAOYSA-N

Niaprazine(INN) (brand nameNopron) is asedative-hypnoticdrugof thephenylpiperazinegroup.[1][2]It has been used in the treatment ofsleep disturbancessince the early 1970s in severalEuropeancountries includingFrance,Italy,andLuxembourg.[3][4]It is commonly used with children and adolescents on account of its favorablesafetyandtolerabilityprofile and lack ofabuse potential.[5][6][7][8][9][10]

Originally believed to act as anantihistamineandanticholinergic,[11]niaprazine was later discovered to have low or nobindingaffinityfor theH1andmACh receptors(Ki= > 1 μM), and was instead found to act as apotentandselective5-HT2Aandα1-adrenergic receptorantagonist(Ki= 75 nM and 86 nM, respectively).[12]It possesses low or no affinity for the5-HT1A,5-HT2B,D2,andβ-adrenergic,as well as atSERTandVMAT(Ki= all > 1 μM), but it does have some affinity for theα2-adrenergic receptor(Ki= 730 nM).[12]

Niaprazine has been shown tometabolizeto the compoundpara-fluorophenylpiperazine(pFPP) in a similar manner to howtrazodoneandnefazodonemetabolize tometa-chlorophenylpiperazine(mCPP).[13][14]It is unclear what role, if any,pFPP plays in the clinical effects of niaprazine.[12]However, from animal studies it is known thatpFPP, unlike niaprazine, does not produce sedative effects, and instead exerts a behavioral profile indicative ofserotonergicactivation.[13]

Synthesis

[edit]

AMannich reactionusing 4-fluorophenylpiperazine (1),1,3,5-trioxane(2) andacetonegives theketone(4). Reaction withhydroxylamineproduces theoxime,(5), which isreducedwithlithium aluminium hydrideto give theamine(6).Amideformation withnicotinic acid(7), activated as itsacid chloride,yields nilaprazine.[15][16]

References

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  1. ^Elks J (14 November 2014).The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies.Springer. pp. 862–.ISBN978-1-4757-2085-3.
  2. ^Kent A, Billiard M (2003).Sleep: physiology, investigations, and medicine.New York: Kluwer Academic/Plenum.ISBN978-0-306-47406-4.
  3. ^Swiss Pharmaceutical Society (2000).Index Nominum 2000: International Drug Directory (Book with CD-ROM).Boca Raton: Medpharm Scientific Publishers.ISBN978-3-88763-075-1.
  4. ^Triggle DJ (1996).Dictionary of Pharmacological Agents.Boca Raton: Chapman & Hall/CRC.ISBN978-0-412-46630-4.
  5. ^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.PMID2958783.
  6. ^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.PMID2903572.
  7. ^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.7(6): 332–5.doi:10.1007/bf00304832.PMID1837245.S2CID35908448.
  8. ^Montanari G, Schiaulini P, Covre A, Steffan A, Furlanut M (1992). "Niaprazine vs chlordesmethyldiazepam in sleep disturbances in pediatric outpatients".Pharmacological Research.25(Suppl 1): 83–4.doi:10.1016/1043-6618(92)90551-l.PMID1354861.
  9. ^Younus M, Labellarte MJ (2002)."Insomnia in children: when are hypnotics indicated?".Paediatric Drugs.4(6): 391–403.doi:10.2165/00128072-200204060-00006.PMID12038875.S2CID33340367.
  10. ^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.PMID16700077.S2CID24273650.
  11. ^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.PMID4401719.
  12. ^abcScherman 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.PMID2853885.S2CID40566589.
  13. ^abKeane 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.PMID6460945.S2CID22310059.
  14. ^Garattini S, Mennini T (1988)."Critical notes on the specificity of drugs in the study of metabolism and functions of brain monoamines".International Review of Neurobiology.29:259–80.doi:10.1016/s0074-7742(08)60089-6.ISBN9780123668295.PMID3042665.
  15. ^US patent 3712893,J Simond, J Moleyre, R Mauvernay, N Busch, "Butyl-piperazine derivatives", issued 1973-01-23, assigned to Centre Europeen de Recherches Mauvernay
  16. ^"Niaprazine".Pharmaceutical Substances.Thieme.Retrieved2024-07-17.
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