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{{drugbox |
{{Drugbox
| IUPAC_name       = N-[4-[4-(4-fluorophenyl)piperazin-1-yl]butan-2-yl]pyridine-3-carboxamide
| IUPAC_name = ''N''-{4-[4-(4-fluorophenyl)piperazin- 1-yl]butan- 2-yl}pyridine- 3-carboxamide
| image             = Niaprazine.png
| image = Niaprazine.svg
| CAS_number        = 27367-90-4
 
| ATC_prefix        = N05
<!--Clinical data-->
| ATC_suffix        = CM16
| tradename =   
| PubChem          = 71919
| Drugs.com = {{drugs.com|international|niaprazine}}
| DrugBank          =
| pregnancy_category =   
| C = 20 | H = 25 | F = 1 | N = 4 | O = 1
| legal_status = Rx-only
| molecular_weight  = 356.437
| bioavailability  =
| protein_bound    =
| metabolism        =
| elimination_half-life = 4.53 +- 0.86 hours
| excretion        =
| pregnancy_AU      =  <!-- A / B1 / B2 / B3 / C / D / X -->
| pregnancy_US      =  <!-- A / B            / C / D / X -->
| pregnancy_category=
| legal_AU          =  <!-- Unscheduled / S2 / S3 / S4 / S5 / S6 / S7 / S8 / S9 -->
| legal_CA          =  <!--            / Schedule I, II, III, IV, V, VI, VII, VIII -->
| legal_UK          =  <!-- GSL        / P      / POM / CD / Class A, B, C -->
| legal_US          = <!-- OTC                  / Rx-only / Schedule I, II, III, IV, V -->
| legal_status      =
| routes_of_administration = Oral
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
| metabolism = 
| elimination_half-life = ~4.5 hours
| excretion = 
<!--Identifiers-->
| CAS_number = 27367-90-4
| ATC_prefix = N05
| ATC_suffix = CM16
| PubChem = 71919
| ChemSpiderID = 64930
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = R2H3YN6E3L
| KEGG = D07333
<!--Chemical data-->
| C=20 | H=25 | F=1 | N=4 | O=1
| molecular_weight = 356.437 g/mol
| smiles = Fc3ccc(N2CCN(CCC(NC(=O)c1cccnc1)C)CC2)cc3
}}
}}


{{SI}}
'''Niaprazine''' ('''Nopron''') is a [[sedative]]-[[hypnotic]] [[drug]] of the [[phenylpiperazine]] class.<ref name="isbn0-306-47406-9">{{cite book | author = Kent, Angela; M. Billiard | title = Sleep: physiology, investigations, and medicine | publisher = Kluwer Academic/Plenum | location = New York | year = 2003 | pages = | isbn = 0-306-47406-9 | oclc = | doi = | url = http://books.google.com/?id=IorPrIY6dOYC&lpg=PA291&vq=niaprazine&pg=PA291#v=onepage&q}}</ref> It has been used in the treatment of [[sleep disorder|sleep disturbance]]s since the early 1970s in several [[Europe]]an countries, including [[France]], [[Italy]], and [[Luxembourg]].<ref name="isbn3-88763-075-0">{{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 | pages = | isbn = 3-88763-075-0 | oclc = | doi = | url = http://books.google.com/?id=5GpcTQD_L2oC&lpg=PA726&dq=niaprazine&pg=PA726#v=onepage&q}}</ref><ref name="isbn0-412-46630-9">{{cite book | author = David J. Triggle | title = Dictionary of Pharmacological Agents | publisher = Chapman & Hall/CRC | location = Boca Raton | year = 1996 | pages = | isbn = 0-412-46630-9 | oclc = | doi = | url = http://books.google.com/?id=A0THacd46ZsC&lpg=PA1418&dq=niaprazine&pg=PA1418#v=onepage&q}}</ref> It is commonly used with children and adolescents on account of its favorable [[safety]] and [[tolerability]] profile and lack of [[abuse potential]].<ref name="pmid2958783">{{cite journal | author = Franzoni E, Masoni P, Mambelli M, Marzano P, Donati C | title = [Niaprazine in behavior disorders in children. Double-blind comparison with placebo] | language = Italian | journal = La Pediatria Medica E Chirurgica : Medical and Surgical Pediatrics | volume = 9 | issue = 2 | pages = 185–7 | year = 1987 | pmid = 2958783 | doi = | url = }}</ref><ref name="pmid2903572">{{cite journal | author = Bodiou C, Bavoux F | title = [Niaprazine and side effects in pediatrics. Cooperative evaluation of French centers of pharmacovigilance] | language = French | journal = Thérapie | volume = 43 | issue = 4 | pages = 307–11 | year = 1988 | pmid = 2903572 | doi = | url = }}</ref><ref name="pmid1837245">{{cite journal | author = 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 : ChNS : Official Journal of the International Society for Pediatric Neurosurgery | volume = 7 | issue = 6 | pages = 332–5 |date=October 1991 | pmid = 1837245 | doi = 10.1007/bf00304832| url = }}</ref><ref name="pmid1354861">{{cite journal | author = Montanari G, Schiaulini P, Covre A, Steffan A, Furlanut M | title = Niaprazine vs chlordesmethyldiazepam in sleep disturbances in pediatric outpatients | journal = Pharmacological Research : the Official Journal of the Italian Pharmacological Society | volume = 25 Suppl 1 | issue = | pages = 83–4 | year = 1992 | pmid = 1354861 | doi = 10.1016/1043-6618(92)90551-l| url = }}</ref><ref name="pmid12038875">{{cite journal | author = 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| url = http://content.wkhealth.com/linkback/openurl?issn=1174-5878&volume=4&issue=6&spage=391}}</ref><ref name="pmid16700077">{{cite journal | author = Mancini J, Thirion X, Masut A, ''et al.'' | 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}}</ref>


==Overview==
Originally believed to act as an [[antihistamine]] and [[anticholinergic]],<ref name="pmid4401719">{{cite journal | author = Duchene-Marullaz P, Rispat G, Perriere JP, Hache J, Labrid C | title = [Some pharmacodynamical properties of niaprazine, a new antihistaminic agent] | language = French | journal = Thérapie | volume = 26 | issue = 6 | pages = 1203–9 | year = 1971 | pmid = 4401719 | doi = | url = }}</ref> niaprazine was later discovered to have no significant [[binding (molecular)|binding]] [[affinity (pharmacology)|affinity]] for either the [[H1 receptor|H<sub>1</sub>]] or the [[muscarinic acetylcholine receptor|mACh receptor]]s (K<sub>i</sub> = > 1 μM), and was instead found to act as a [[potency (pharmacology)|potent]] and [[binding selectivity|selective]] [[5-HT2A receptor|5-HT<sub>2A</sub>]] and [[alpha-1 adrenergic receptor|α<sub>1</sub>-adrenergic receptor]] [[receptor antagonist|antagonist]] (K<sub>i</sub> = 75 nM and 86 nM, respectively).<ref name="pmid2853885">{{cite journal | author = Scherman D, Hamon M, Gozlan H, ''et al.'' | 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| url = }}</ref> It is virtually inactive at [[5-HT1A receptor|5-HT<sub>1A</sub>]], [[5-HT2B receptor|5-HT<sub>2B</sub>]], [[D2 receptor|D<sub>2</sub>]], and [[beta-adrenergic receptor|β-adrenergic]], as well as at [[serotonin transporter|SERT]] and [[vesicular monoamine transporter|VMAT]] (K<sub>i</sub> = all > 1 μM), but it does have some weak affinity for the [[alpha-2 adrenergic receptor|α<sub>2</sub>-adrenergic receptor]] (K<sub>i</sub> = 730 nM),<ref name="pmid2853885" /> likely acting as an antagonist there as well.
Niaprazine (Nopron) is a [[piperazine]] derivative drug which acts as a sedating [[antihistamine]]. It was invented in the 1970s <ref> Duchene-Marullaz P, Rispat G, Perriere JP, Hache J, Labrid C. Some pharmacodynamical properties of niaprazine, a new antihistaminic agent. (French) Therapie. 1971 Nov-Dec;26(6):1203-9. </ref>, and is used in France, Italy and other european countries. It is mainly prescribed for its relatively strong [[sedative]] effects rather than as an antihistamine, and is used mainly for treating [[autism]] <ref> Rossi PG, Posar A, Parmeggiani A, Pipitone E, D'Agata M. Niaprazine in the treatment of autistic disorder. Journal of Child Neurology. 1999 Aug;14(8):547-50. </ref> and [[insomnia]] <ref> Younus M, Labellarte MJ. Insomnia in children: when are hypnotics indicated? Paediatric Drugs. 2002;4(6):391-403. </ref> in children and adolescents. Common side effects are: sedation during the day (especially during the first few days of treatment) and [[dizziness]].


Niaprazine has been shown to [[metabolize]] to the compound [[para-Fluorophenylpiperazine|''p''FPP]] in a similar manner to how [[trazodone]] and [[nefazodone]] metabolize to [[meta-Chlorophenylpiperazine|''m''CPP]].<ref name="pmid6460945">{{cite journal | author = 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| url = }}</ref><ref name="isbn0-12-366829-8">{{Cite book | title = International review of neurobiology | year = 1988 | publisher = Academic Press | location = New York  | isbn = 0-12-366829-8 | pages = | url = http://books.google.com/?id=Uf_BWXKXW2cC&lpg=PA274&dq=niaprazine&pg=PA274#v=onepage&q}}</ref> It is unclear what role, if any, ''p''FPP plays in the clinical effects of niaprazine.<ref name="pmid2853885" /> However, from animal studies it is known that ''p''FPP, unlike niaprazine, does not produce sedative effects, and instead exerts a behavioral profile indicative of [[serotonergic]] activation.<ref name="pmid6460945" />
== See also ==
* [[Phenylpiperazine]]


== References ==
== References ==
{{reflist|2}}
{{Reflist}}
{{Hypnotics and sedatives}}
{{antihistamines}}


{{Hypnotics}}
{{Adrenergics}}
{{Serotonergics}}
{{Piperazines}}


[[Category:Carboxamides]]
[[Category:Organofluorides]]
[[Category:Piperazines]]
[[Category:Piperazines]]
 
[[Category:Pyridines]]
{{WikiDoc Sources}}
{{WH}}

Revision as of 15:25, 13 April 2015

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

| tradename = | Drugs.com = International Drug Names | pregnancy_category = | legal_status = Rx-only | routes_of_administration = Oral

| 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 =  ☑Y | UNII = R2H3YN6E3L | KEGG = D07333

| C=20 | H=25 | F=1 | N=4 | O=1 | molecular_weight = 356.437 g/mol | smiles = Fc3ccc(N2CCN(CCC(NC(=O)c1cccnc1)C)CC2)cc3 }}

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

References

  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. ↑ 11.0 11.1 11.2 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. ↑ 12.0 12.1 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.

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