Niaprazine

Last updated

Niaprazine
Niaprazine.svg
Clinical data
Trade names Nopron
Other namesCERM-1709
AHFS/Drugs.com International Drug Names
Routes of
administration
Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life ~4.5 hours
Identifiers
  • N-{4-[4-(4-fluorophenyl)piperazin- 1-yl]butan- 2-yl}pyridine- 3-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
ECHA InfoCard 100.044.014 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C20H25FN4O
Molar mass 356.445 g·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 name Nopron) is a sedative-hypnotic drug of the phenylpiperazine group. [1] [2] It has been used in the treatment of sleep disturbances since the early 1970s in several European countries including France, Italy, and Luxembourg. [3] [4] It is commonly used with children and adolescents on account of its favorable safety and tolerability profile and lack of abuse potential. [5] [6] [7] [8] [9] [10]

Originally believed to act as an antihistamine and anticholinergic, [11] niaprazine was later discovered to have low or no binding affinity for the H1 and 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). [12] It possesses low or no affinity for the 5-HT1A, 5-HT2B, D2, and β-adrenergic, as well as at SERT and VMAT (Ki = all > 1 μM), but it does have some affinity for the α2-adrenergic receptor (Ki = 730 nM). [12]

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). [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 that pFPP, unlike niaprazine, does not produce sedative effects, and instead exerts a behavioral profile indicative of serotonergic activation. [13]

Synthesis

Niaprazine synthesis.svg

A Mannich reaction using 4-fluorophenylpiperazine (1), 1,3,5-trioxane (2) and acetone gives the ketone (4). Reaction with hydroxylamine produces the oxime, (5), which is reduced with lithium aluminium hydride to give the amine (6). Amide formation with nicotinic acid (7), activated as its acid chloride, yields nilaprazine. [15] [16]

Related Research Articles

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<span class="mw-page-title-main">Receptor antagonist</span> Type of receptor ligand or drug that blocks a biological response

A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of receptor proteins. They are sometimes called blockers; examples include alpha blockers, beta blockers, and calcium channel blockers. In pharmacology, antagonists have affinity but no efficacy for their cognate receptors, and binding will disrupt the interaction and inhibit the function of an agonist or inverse agonist at receptors. Antagonists mediate their effects by binding to the active site or to the allosteric site on a receptor, or they may interact at unique binding sites not normally involved in the biological regulation of the receptor's activity. Antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding. The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors.

<span class="mw-page-title-main">Chlorphenamine</span> Antihistamine used to treat allergies

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<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

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<span class="mw-page-title-main">Doxylamine</span> First-generation antihistamine used as a short-term sedative and hypnotic (sleep aid)

Doxylamine is an antihistamine medication used to treat insomnia and allergies, and—in combination with pyridoxine (vitamin B6)—to treat morning sickness in pregnant women. It is available over-the-counter and is typically sold under such brand names as Equate, Unisom, or ZzzQuil, among others; and it is used in nighttime cold medicines (e.g., NyQuil) and pain medications containing acetaminophen and/or codeine to help with sleep. The medication is delivered chemically by the salt doxylamine succinate and is taken by mouth. Doxylamine and other first-generation antihistamines are the most widely used sleep medications in the world.Typical side effects of doxylamine (at recommended doses) include dizziness, drowsiness, grogginess, and dry mouth, among others.

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Quazepam, sold under the brand name Doral among others, is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is used for the treatment of insomnia, including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.

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<i>meta</i>-Chlorophenylpiperazine Stimulant

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<span class="mw-page-title-main">Serotonin antagonist and reuptake inhibitor</span> Class of drug

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