Niaprazine

{{Short description|Sedative-hypnotic medication}}

{{cs1 config|name-list-style=vanc}}

{{Drugbox

| IUPAC_name = N-{4-[4-(4-fluorophenyl)piperazin- 1-yl]butan- 2-yl}pyridine- 3-carboxamide

| image = Niaprazine.svg

| width = 250px

| tradename = Nopron

| Drugs.com = {{drugs.com|international|niaprazine}}

| pregnancy_category =

| legal_status = Rx-only

| routes_of_administration = Oral

| bioavailability =

| protein_bound =

| metabolism =

| elimination_half-life = ~4.5 hours

| excretion =

| CAS_number = 27367-90-4

| ATC_prefix = N05

| ATC_suffix = CM16

| PubChem = 71919

| ChemSpiderID = 64930

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = R2H3YN6E3L

| KEGG = D07333

| synonyms = CERM-1709

| StdInChI = 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)

| StdInChIKey = RSKQGBFMNPDPLR-UHFFFAOYSA-N

| C=20 | H=25 | F=1 | N=4 | O=1

| smiles = Fc3ccc(N2CCN(CCC(NC(=O)c1cccnc1)C)CC2)cc3

}}

Niaprazine (INN; brand name Nopron) is a sedative-hypnotic drug of the phenylpiperazine group.{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA862|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=862–}}{{cite book | vauthors = Kent A, Billiard M| title = Sleep: physiology, investigations, and medicine | publisher = Kluwer Academic/Plenum | location = New York | year = 2003 | isbn = 978-0-306-47406-4 | url = https://books.google.com/books?id=IorPrIY6dOYC&q=niaprazine&pg=PA291}} It has been used in the treatment of sleep disturbances since the early 1970s in several European countries including France, Italy, and Luxembourg.{{cite book | author = Swiss Pharmaceutical Society | title = Index Nominum 2000: International Drug Directory (Book with CD-ROM) | publisher = Medpharm Scientific Publishers | location = Boca Raton | year = 2000 | isbn = 978-3-88763-075-1 | url = https://books.google.com/books?id=5GpcTQD_L2oC&q=niaprazine&pg=PA726}}{{cite book | vauthors = Triggle DJ | title = Dictionary of Pharmacological Agents | publisher = Chapman & Hall/CRC | location = Boca Raton | year = 1996 | isbn = 978-0-412-46630-4 | url = https://books.google.com/books?id=A0THacd46ZsC&q=niaprazine&pg=PA1418}} It is commonly used with children and adolescents on account of its favorable safety and tolerability profile and lack of abuse potential.{{cite journal |vauthors=Franzoni E, Masoni P, Mambelli M, Marzano P, Donati C | title = [Niaprazine in behavior disorders in children. Double-blind comparison with placebo] | language = it | journal = La Pediatria Medica e Chirurgica: Medical and Surgical Pediatrics | volume = 9 | issue = 2 | pages = 185–7 | year = 1987 | pmid = 2958783 }}{{cite journal |vauthors=Bodiou C, Bavoux F | title = [Niaprazine and side effects in pediatrics. Cooperative evaluation of French centers of pharmacovigilance] | language = fr | journal = Thérapie | volume = 43 | issue = 4 | pages = 307–11 | year = 1988 | pmid = 2903572 }}{{cite journal |vauthors=Ottaviano S, Giannotti F, Cortesi F | title = The effect of niaprazine on some common sleep disorders in children. A double-blind clinical trial by means of continuous home-videorecorded sleep | journal = Child's Nervous System | volume = 7 | issue = 6 | pages = 332–5 |date=October 1991 | pmid = 1837245 | doi = 10.1007/bf00304832| s2cid = 35908448 }}{{cite journal |vauthors=Montanari G, Schiaulini P, Covre A, Steffan A, Furlanut M | title = Niaprazine vs chlordesmethyldiazepam in sleep disturbances in pediatric outpatients | journal = Pharmacological Research | volume = 25 | pages = 83–4 | year = 1992 | issue = Suppl 1 | pmid = 1354861 | doi = 10.1016/1043-6618(92)90551-l}}{{cite journal |vauthors=Younus M, Labellarte MJ | title = Insomnia in children: when are hypnotics indicated? | journal = Paediatric Drugs | volume = 4 | issue = 6 | pages = 391–403 | year = 2002 | pmid = 12038875 | doi = 10.2165/00128072-200204060-00006| s2cid = 33340367 | url = https://dx.doi.org/10.2165%2F00128072-200204060-00006}}{{cite journal |vauthors=Mancini J, Thirion X, Masut A, etal | title = Anxiolytics, hypnotics, and antidepressants dispensed to adolescents in a French region in 2002 | journal = Pharmacoepidemiology and Drug Safety | volume = 15 | issue = 7 | pages = 494–503 |date=July 2006 | pmid = 16700077 | doi = 10.1002/pds.1258| s2cid = 24273650 }}

Originally believed to act as an antihistamine and anticholinergic,{{cite journal |vauthors=Duchene-Marullaz P, Rispat G, Perriere JP, Hache J, Labrid C | title = [Some pharmacodynamical properties of niaprazine, a new antihistaminic agent] | language = fr | journal = Thérapie | volume = 26 | issue = 6 | pages = 1203–9 | year = 1971 | pmid = 4401719 }} niaprazine was later discovered to have low or no binding affinity for the H₁ and 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).{{cite journal |vauthors=Scherman D, Hamon M, Gozlan H, etal | title = Molecular pharmacology of niaprazine | journal = Progress in Neuro-psychopharmacology & Biological Psychiatry | volume = 12 | issue = 6 | pages = 989–1001 | year = 1988 | pmid = 2853885 | doi = 10.1016/0278-5846(88)90093-0| s2cid = 40566589 }} It possesses low or no affinity for the 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 affinity for the α₂-adrenergic receptor (K_i = 730 nM).

Niaprazine has been shown to metabolize to the compound para-fluorophenylpiperazine (pFPP) in a similar manner to how trazodone and nefazodone metabolize to meta-chlorophenylpiperazine (mCPP).{{cite journal |vauthors=Keane PE, Strolin Benedetti M, Dow J | title = The effect of niaprazine on the turnover of 5-hydroxytryptamine in the rat brain | journal = Neuropharmacology | volume = 21 | issue = 2 | pages = 163–9 |date=February 1982 | pmid = 6460945 | doi = 10.1016/0028-3908(82)90157-5| s2cid = 22310059 }}{{cite journal | vauthors = Garattini S, Mennini T | title = Critical notes on the specificity of drugs in the study of metabolism and functions of brain monoamines | journal = International Review of Neurobiology | volume = 29 | pages = 259–80 | date = 1988 | pmid = 3042665 | doi = 10.1016/s0074-7742(08)60089-6 | isbn = 9780123668295 | url = https://books.google.com/books?id=Uf_BWXKXW2cC&q=niaprazine&pg=PA274 }} It is unclear what role, if any, pFPP plays in the clinical effects of niaprazine. 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.