Niaprazine: Difference between revisions
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{{Drugbox |
{{Drugbox |
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| IUPAC_name = ''N''- |
| IUPAC_name = ''N''-{4-[4-(4-fluorophenyl)piperazin-1-yl]butan-2-yl}pyridine-3-carboxamide |
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| image = Niaprazine.svg |
| image = Niaprazine.svg |
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| CAS_number = 27367-90-4 |
| CAS_number = 27367-90-4 |
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| ATC_suffix = CM16 |
| ATC_suffix = CM16 |
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| PubChem = 71919 |
| PubChem = 71919 |
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| ChemSpiderID = 64930 |
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| C = 20 | H = 25 | F = 1 | N = 4 | O = 1 |
| C = 20 | H = 25 | F = 1 | N = 4 | O = 1 |
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| molecular_weight = 356.437 g/mol |
| molecular_weight = 356.437 g/mol |
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| smiles = Fc3ccc(N2CCN(CCC(NC(=O)c1cccnc1)C)CC2)cc3 |
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| metabolism = |
| metabolism = |
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| elimination_half-life = ~4.5 hours |
| elimination_half-life = ~4.5 hours |
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'''Niaprazine''' ('''Nopron''') is a [[sedative]]-[[hypnotic]] [[drug]] of the [[phenylpiperazine]] class. It has been used in the treatment of [[sleep disorder|sleep disturbance]]s since the early 1970s in some [[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/books?id=5GpcTQD_L2oC&lpg=PA726&dq=niaprazine&as_brr=3&pg=PA726#v=onepage&q&f=false}}</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/books?id=A0THacd46ZsC&lpg=PA1418&dq=niaprazine&lr&as_brr=3&pg=PA1418#v=onepage&q&f=false}}</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 | year = 1991 | month = October | pmid = 1837245 | doi = | 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 = | 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 = | 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 | year = 2006 | month = July | pmid = 16700077 | doi = 10.1002/pds.1258 | url = http://dx.doi.org/10.1002/pds.1258}}</ref> |
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'''Niaprazine''' ('''Nopron''') is a [[drug]] of the [[phenylpiperazine]] class which acts as a sedating [[antihistamine]] as well as [[anticholinergic]]. 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. |
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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. |
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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> = >1,000 nM), 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 = | url = }}</ref> It is 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 the [[serotonin transporter|SERT]] and [[vesicular monoamine transporter|VMAT]]s (K<sub>i</sub> = all >1,000), 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">{{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 = | url = }}</ref> |
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== Side effects == |
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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 | year = 1982 | month = February | pmid = 6460945 | doi = | url = }}</ref> It is unclear what role, if any, ''p''FPP plays in the clinical effects of niaprazine.<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 = | url = }}</ref> |
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Common side effects are: sedation during the day (especially during the first few days of treatment) and [[dizziness]]. Less common side effect is headache during the day. |
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== Method of action == |
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Niaprazine acts as a [[potency (pharmacology)|potent]] [[inverse agonist]] of the [[H1 receptor|H<sub>1</sub> receptor]] and [[receptor antagonist|antagonist]], and is also a non-[[binding selectivity|selective]] [[serotonin receptor]] [[agonist]] and [[serotonin releasing agent|releasing agent]] via its [[activity (chemistry)|active]] [[metabolite]] [[pFPP]]. It also antagonizes [[muscarinic acetylcholine receptor|mACh receptor]]s. |
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== See also == |
== See also == |
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{{Hypnotics}} |
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{{Piperazines}} |
{{Piperazines}} |
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[[Category:Piperazines]] |
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Revision as of 20:57, 14 April 2010
{{Drugbox | IUPAC_name = N-{4-[4-(4-fluorophenyl)piperazin-1-yl]butan-2-yl}pyridine-3-carboxamide | image = Niaprazine.svg | CAS_number = 27367-90-4 | ATC_prefix = N05 | ATC_suffix = CM16 | PubChem = 71919 | ChemSpiderID = 64930 | 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 | metabolism = | elimination_half-life = ~4.5 hours | excretion = | pregnancy_category = | legal_status = Rx-only | routes_of_administration = Oral }}
Niaprazine (Nopron) is a sedative-hypnotic drug of the phenylpiperazine class. It has been used in the treatment of sleep disturbances since the early 1970s in some European countries, including France, Italy, and Luxembourg.[1][2] It is commonly used with children and adolescents on account of its favorable safety and tolerability profile and lack of abuse potential.[3][4][5][6][7][8]
Originally believed to act as an antihistamine and anticholinergic,[9] niaprazine was later discovered to have no significant binding affinity for either the H1 or the mACh receptors (Ki = >1,000 nM), 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).[10] It is inactive at 5-HT1A, 5-HT2B, D2, and β-adrenergic, as well as at the SERT and VMATs (Ki = all >1,000), but it does have some weak affinity for the α2-adrenergic receptor (Ki = 730 nM).[10]
Niaprazine has been shown to metabolize to the compound pFPP in a similar manner to how trazodone and nefazodone metabolize to mCPP.[11] It is unclear what role, if any, pFPP plays in the clinical effects of niaprazine.[10]
See also
References
- ^ Swiss Pharmaceutical Society (2000). Index Nominum 2000: International Drug Directory (Book with CD-ROM). Boca Raton: Medpharm Scientific Publishers. ISBN 3-88763-075-0.
- ^ David J. Triggle (1996). Dictionary of Pharmacological Agents. Boca Raton: Chapman & Hall/CRC. ISBN 0-412-46630-9.
- ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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.
- ^ Ottaviano S, Giannotti F, Cortesi F (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.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Younus M, Labellarte MJ (2002). "Insomnia in children: when are hypnotics indicated?". Paediatric Drugs. 4 (6): 391–403. PMID 12038875.
- ^ Mancini J, Thirion X, Masut A; et al. (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.
{{cite journal}}: Explicit use of et al. in:|author=(help); Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ 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.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ 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. PMID 2853885.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - ^ Keane PE, Strolin Benedetti M, Dow J (1982). "The effect of niaprazine on the turnover of 5-hydroxytryptamine in the rat brain". Neuropharmacology. 21 (2): 163–9. PMID 6460945.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)