Perlapine

{{Short description|Sedative and hypnotic medication}}

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{{Infobox drug

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| IUPAC_name = 6-(4-Methylpiperazin-1-yl)-11H-benzo[c][1]benzazepine

| image = Perlapine.svg

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| tradename = Hypnodine, Pipnodine

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| CAS_number = 1977-11-3

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| PubChem = 16106

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| ChemSpiderID = 15291

| UNII = 4N8UJJ27IM

| KEGG = D01438

| ChEBI = 31983

| ChEMBL = 340801

| synonyms = AW-14233; HF-2333; MP-11; PLP 100-127; 6-(4-Methyl-1-piperazinyl)morphanthridine

| C=19 | H=21 | N=3

| SMILES = CN1CCN(CC1)C2=NC3=CC=CC=C3CC4=CC=CC=C42

| StdInChI_Ref =

| StdInChI = 1S/C19H21N3/c1-21-10-12-22(13-11-21)19-17-8-4-2-6-15(17)14-16-7-3-5-9-18(16)20-19/h2-9H,10-14H2,1H3

| StdInChIKey_Ref =

| StdInChIKey = PWRPUAKXMQAFCJ-UHFFFAOYSA-N

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Perlapine, sold under the brand names Hypnodine and Pipnodine, is a hypnotic and sedative of the tricyclic group which is marketed in Japan.{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA811|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=811–}} It acts primarily as a potent antihistamine,{{cite book | vauthors = Leysen JE, Niemegeers CJ | chapter = Neuroleptics | title = Alterations of Metabolites in the Nervous System | date = 1985 | pages = 331–361 | location = Boston, MA. | veditors = Lajtha A |chapter-url= https://books.google.com/books?id=dYnSBwAAQBAJ&pg=PA352 |publisher=Springer Science & Business Media|isbn=978-1-4757-6740-7 }} and also has anticholinergic, antiserotonergic,{{cite journal | vauthors = Megens AA, Kennis LE | title = Risperidone and related 5HT2/D2 antagonists: a new type of antipsychotic agent? | journal = Progress in Medicinal Chemistry | volume = 33 | pages = 185–232 | date = 1996 | pmid = 8776944 | doi = 10.1016/s0079-6468(08)70306-0 | isbn = 9780444823106 }} antiadrenergic, and some antidopaminergic activity.{{cite book| vauthors = Hathway DE |title=Foreign Compound Metabolism in Mammals|url=https://books.google.com/books?id=UHAoDwAAQBAJ&pg=PA302|date=31 October 2007|publisher=Royal Society of Chemistry|isbn=978-1-84755-608-0|pages=302–}}{{cite journal | vauthors = Liegeois JF, Bruhwyler J, Rogister F, Delarge J | title = Diarylazepine derivatives as potent atypical neuroleptic drugs: recent advances. | journal = Current Medicinal Chemistry | date = April 1995 | volume = 1 | issue = 6 | pages = 471–501 |publisher=Bentham Science Publishers | doi = 10.2174/092986730106220216114910 | s2cid = 87829622 |url=https://books.google.com/books?id=eMw2LsjQ5PQC&pg=PA489 | url-access = subscription }}{{cite book| vauthors = Barnes TR |title=Antipsychotic Drugs and Their Side-Effects |url=https://books.google.com/books?id=IT2OAgAAQBAJ&pg=PA34|date=22 October 2013|publisher=Elsevier Science|isbn=978-1-4832-8810-9|pages=28, 34}} The drug has relatively weak affinity for the dopamine D₂ receptor ({{abbrlink|IC₅₀|Half-maximal inhibitory concentration}} = 1,803 nM) and, in accordance, is said to be ineffective as an antipsychotic.{{cite book|author=American College of Neuropsychopharmacology|title=Psychopharmacology: a generation of progress|url=https://books.google.com/books?id=c-RsAAAAMAAJ|year=1978|publisher=Raven Press|isbn=978-0-89004-191-8|page=514}} However, it retains higher affinity for the dopamine D₁ receptor ({{abbr|IC₅₀|Half-maximal inhibitory concentration}} = 198 nM). Its {{abbr|IC₅₀|Half-maximal inhibitory concentration}} values are 19 nM for the α₁-adrenergic receptor, 4,945 nM for the α₂-adrenergic receptor, and 70 nM for the serotonin 5-HT_2A receptor. Perlapine is closely related to clotiapine, clozapine, fluperlapine, loxapine, and tilozepine.

Perlapine has been suggested as a potential ligand for certain DREADDs.{{cite journal | vauthors = Thompson KJ, Khajehali E, Bradley SJ, Navarrete JS, Huang XP, Slocum S, Jin J, Liu J, Xiong Y, Olsen RH, Diberto JF, Boyt KM, Pina MM, Pati D, Molloy C, Bundgaard C, Sexton PM, Kash TL, Krashes MJ, Christopoulos A, Roth BL, Tobin AB | display-authors = 6 | title = DREADD Agonist 21 Is an Effective Agonist for Muscarinic-Based DREADDs in Vitro and in Vivo | journal = ACS Pharmacology & Translational Science | volume = 1 | issue = 1 | pages = 61–72 | date = September 2018 | pmid = 30868140 | pmc = 6407913 | doi = 10.1021/acsptsci.8b00012 }}{{cite journal | vauthors = Chen X, Choo H, Huang XP, Yang X, Stone O, Roth BL, Jin J | title = The first structure-activity relationship studies for designer receptors exclusively activated by designer drugs | journal = ACS Chemical Neuroscience | volume = 6 | issue = 3 | pages = 476–484 | date = March 2015 | pmid = 25587888 | pmc = 4368042 | doi = 10.1021/cn500325v | author6-link = Bryan Roth }}