pirlindole
{{Short description|Chemical compound}}
{{cs1 config|name-list-style=vanc}}
{{Drugbox
| IUPAC_name = 8-methyl-2,3,3a,4,5,6-hexahydro-1H-pyrazino[3,2,1-jk]carbazole
| image = Pirlindole structure.svg
| width = 100px
| tradename = Lifril, Pirazidol
| pregnancy_category =
| legal_status = Rx-only
| routes_of_administration = By mouth
| bioavailability = 20–30%
| protein_bound = 95%
| metabolism = hepatic
| onset = 2–8 hours
| elimination_half-life = up to 8 days {{cite book | vauthors = Pöldinger W | date = 1985 | chapter = Pirlindole: results of an open clinical study in out-patients and of a double-blind study against maprotiline. | title = Psychiatry the State of the Art | pages = 283–289 | publisher = Springer | location = Boston, MA. | isbn = 978-1-4613-2363-1 | doi = 10.1007/978-1-4613-2363-1_44 }}
| excretion = urine (50–70%), feces (25–45%)
| IUPHAR_ligand = 6638
| CAS_number = 60762-57-4
| ATC_prefix = None
| ATC_suffix =
| PubChem = 68802
| ChemSpiderID = 62039
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB09244
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = V39YPH45FZ
| KEGG = D08392
| ChEMBL = 32350
| C = 15
| H = 18
| N = 2
| smiles = CC1=CC2=C(C=C1)N3CCNC4C3=C2CCC4
}}
Pirlindole, sold under the brand names Lifril and Pyrazidol, is mainly a reversible inhibitor of monoamine oxidase A (RIMA) and secondly a serotonin–norepinephrine reuptake inhibitor (SNRI) which was developed and is used in Russia as an antidepressant.{{cite journal | vauthors = Bruhwyler J, Liégeois JF, Géczy J | title = Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties | journal = Pharmacological Research | volume = 36 | issue = 1 | pages = 23–33 | date = July 1997 | pmid = 9368911 | doi = 10.1006/phrs.1997.0196 }} It is structurally and pharmacologically related to metralindole.
Synthesis
[[File:Pirlindole synthesis.svg|thumb|400px|center|Synthesis:{{cite journal | title = Tetrahydrocarbazole derivatives and their antitubercular activity in vitro. I. N-Substituted hexahydro-1H-pyrazino[3,2,1-j,k]carbazoles
| vauthors = Filitis LN, Fedotova OA, Akalaeva TV, Bokanov AI, Ivanov PY, Neustroeva VD, Nyrkova VG, Pershin GN, Shvedov VI | journal = Khimiko-Farmatsevticheskii Zhurnal | date = 1986 | volume = 20 | issue = 3 | pages = 300–303 | language = Russian }}{{cite journal | vauthors= Ivanov PY, Alekseeva LM, Bokanov AI, Shvedov VI, Sheinker YN | journal=Pharmaceutical Chemistry Journal | title=New approach to the synthesis of pyrazidol | volume=21 | issue=1 | pages=62–65 | date= January 1987 | doi=10.1007/BF00764890| s2cid=22179419 }}.{{cite journal | vauthors=De Tullio P, Felikidis A, Pirotte B, Liégeois JF, Stachow M, Delarge J, Ceccato A, Hubert P, Crommen J, Géczy J | journal=Helvetica Chimica Acta | title=First Preparative Enantiomer Resolution of Pirlindole, a Potent Antidepressant Drug | volume=81 | issue=3–4 | pages=539–547 | date= 1998 | issn=0018-019X | doi=10.1002/hlca.19980810307}}. Patents:, {{Cite patent|FR|2132514}} (1972 to Inst Im Sergo); CA, 78, 124628rMassimo Ferrari, et al. {{Cite patent|EP|1044976}} (2002 to Erregierre SpA).Massimo Ferrari, et al. CZ20001348 (2000).{{Cite patent|DE|2114230}}{{Cite patent|GB|1340529}} Sino:Chen Weidong, et al. {{Cite patent|CN|110950873}} (2020 to Henan University). Enantiomers:Carla Patricia Da Costa Pereira Rosa, et al. {{Cite patent|WO|2018193415}} (to Tecnimede Sociedade Tecnico Medicinal SA).]]
The Fischer indole synthesis between p-Tolylhydrazine Hydrochloride [637-60-5] (1) and 1,2-Cyclohexanedione [765-87-7] (2) gives 6-methyl-2,3,4,9-tetrahydrocarbazol-1-one [3449-48-7] (3). Imine formation with ethanolamine [141-43-5] (4) gives [https://pubchem.ncbi.nlm.nih.gov/compound/2838578 CID:2838578] (5). Halogenation with phosphorus oxychloride gives (6).{{cite web | title = N-(2-chloroethyl)-6-methyl-2,3,4,9-tetrahydrocarbazol-1-imine | url = https://pubchem.ncbi.nlm.nih.gov/compound/135418359 | work = PubMed | publisher = U.S. National Library of Medicine }} Intramolcular alkylation with the indole nitrogen resulted in Dehydropirlindole [75804-32-9] (7). Reduction of the imine with sodium borohydride completes the synthesis of pirlindole (8).
See also
References
{{Reflist}}
{{Antidepressants}}
{{Anxiolytics}}
{{Monoamine metabolism modulators}}
Category:Reversible inhibitors of MAO-A
Category:Monoamine oxidase inhibitors
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