Pirlindole free base

• CAT Number: I011993
• CAS Number: 60762-57-4
• Molecular Formula: C15H18N2
• Molecular Weight: 226.323
• Purity: ≥95%
• Solubility: Soluble in DMSO
• Storage: Store at 0-8 °C
• InChI: InChI=1S/C15H18N2/c1-10-5-6-14-12(9-10)11-3-2-4-13-15(11)17(14)8-7-16-13/h5-6,9,13,16H,2-4,7-8H2,1H3
• InChIKey: IWVRVEIKCBFZNF-UHFFFAOYSA-N
• SMILES: CC1=CC2=C(C=C1)N3C4=C2CCCC4NCC3

Pirlindole is a reversible inhibitor of monoamine oxidase A (RIMA) which was developed and is used in Russia as an antidepressant. It is structurally and pharmacologically related to metralindole. Pirlindole is approved in some European and non-European countries for the treatment of depression. Pirlindole has an absolute bioavailability of between 20 and 30% due to an extensive first-pass effect. Orally, the Tmax varies between 2.5 and 6 h in the rat and 0.8 and 2 h in the dog.

Reference

1: Macedo A, Leiria E, Filipe A. Pirlindole in the treatment of depression: a meta-analysis. Clin Drug Investig. 2011;31(1):61-71. doi: 10.2165/11586690-000000000-00000. PubMed PMID: 21053988. 2: Branco JC, Tomé AM, Cruz MR, Filipe A. Pirlindole in the treatment of depression and fibromyalgia syndrome. Clin Drug Investig. 2011 Oct 1;31(10):675-89. doi: 10.2165/11595410-000000000-00000. Review. PubMed PMID: 21877764. 3: Fiedler VB, Buchheim S, Nitz RE, Scholtholt J. Haemodynamic effects of pirlindole, a new tetracyclic antidepressant agent. Arzneimittelforschung. 1983;33(2):244-50. PubMed PMID: 6682664. 4: Boland A, Gérardy J, Mossay D, Seutin V. Pre- and post-treatment with pirlindole and dehydropirlindole protects cultured brain cells against nitric oxide-induced death. Eur J Pharmacol. 2003 Apr 11;466(1-2):21-30. PubMed PMID: 12679138. 5: Bun/’kova KM. [Efficacy and tolerability of clomipramine, pirlindole and escitalopram in the treatment of neurotic level depression]. Zh Nevrol Psikhiatr Im S S Korsakova. 2008;108(3):29-32. Russian. PubMed PMID: 18427538. 6: Medvedev AE, Shvedov VI, Chulkova TM, Fedotova OA, Saederup E, Squires RF. The influence of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase A and GABAA receptor binding. J Neural Transm Suppl. 1998;52:337-42. PubMed PMID: 9564636. 7: Medvedev AE, Shvedov VI, Chulkova TM, Fedotova OA, Saederup E, Squires RF. Effects of the antidepressant pirlindole and its dehydro-derivative on the activity of monoamine oxidase-A and on GABAA receptors. Neurochem Res. 1996 Dec;21(12):1521-6. PubMed PMID: 8953568. 8: Ehlers T, Ritter M. Effects of the tetracyclic antidepressant pirlindole on sensorimotor performance and subjective condition in comparison to imipramine and during interaction of ethanol. Neuropsychobiology. 1984;12(1):48-54. PubMed PMID: 6514177. 9: Bruhwyler J, Liégeois JF, Gérardy J, Damas J, Chleide E, Lejeune C, Decamp E, de Tullio P, Delarge J, Dresse A, Géczy J. Comparative study of pirlindole, a selective RIMA, and its two enantiomers using biochemical and behavioural techniques. Behav Pharmacol. 1998 Dec;9(8):731-7. PubMed PMID: 9890262. 10: Bruhwyler J, Liégeois JF, Géczy J. Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties. Pharmacol Res. 1997 Jul;36(1):23-33. Review. PubMed PMID: 9368911. 11: Ostrowski J, Theumer J, Gärtner W, Resag K, Passing H. Determination of pirlindole in plasma and urine by high-performance liquid chromatography. J Chromatogr. 1984 Jul 13;309(1):115-23. PubMed PMID: 6480758. 12: Tanghe A, Geerts S, Van Dorpe J, Brichard B, Bruhwyler J, Géczy J. Double-blind randomized controlled study of the efficacy and tolerability of two reversible monoamine oxidase A inhibitors, pirlindole and moclobemide, in the treatment of depression. Acta Psychiatr Scand. 1997 Aug;96(2):134-41. PubMed PMID: 9272198. 13: Morais M, Santos PA, Mateus-Pinheiro A, Patrício P, Pinto L, Sousa N, Pedroso P, Almeida S, Filipe A, Bessa JM. The effects of chronic stress on hippocampal adult neurogenesis and dendritic plasticity are reversed by selective MAO-A inhibition. J Psychopharmacol. 2014 Dec;28(12):1178-83. doi: 10.1177/0269881114553646. Epub 2014 Oct 14. PubMed PMID: 25315831. 14: Ceccato A, Hubert P, de Tullio P, Liégeois JF, Felikidis A, Géczy J, Crommen J. Enantiomeric separation of pirlindole by liquid chromatography using different types of chiral stationary phases. J Pharm Biomed Anal. 1998 Dec;18(4-5):605-14. PubMed PMID: 9919961. 15: Ulferts R, de Boer SM, van der Linden L, Bauer L, Lyoo HR, Maté MJ, Lichière J, Canard B, Lelieveld D, Omta W, Egan D, Coutard B, van Kuppeveld FJ. Screening of a Library of FDA-Approved Drugs Identifies Several Enterovirus Replication Inhibitors That Target Viral Protein 2C. Antimicrob Agents Chemother. 2016 Apr 22;60(5):2627-38. doi: 10.1128/AAC.02182-15. Print 2016 May. PubMed PMID: 26856848; PubMed Central PMCID: PMC4862474. 16: Nosengo N. Can you teach old drugs new tricks? Nature. 2016 Jun 16;534(7607):314-6. doi: 10.1038/534314a. PubMed PMID: 27306171. 17: De Wilde JE, Geerts S, Van Dorpe J, Bruhwyler J, Géczy J. A double-blind randomized placebo-controlled study of the efficacy and safety of pirlindole, a reversible monoamine oxidase A inhibitor, in the treatment of depression. Acta Psychiatr Scand. 1996 Dec;94(6):404-10. PubMed PMID: 9020990. 18: Hynson RM, Wouters J, Ramsay RR. Monoamine oxidase A inhibitory potency and flavin perturbation are influenced by different aspects of pirlindole inhibitor structure. Biochem Pharmacol. 2003 Jun 1;65(11):1867-74. PubMed PMID: 12781338. 19: Mashkovsky MD, Andrejeva NI. Pharmacological properties of 2,3,3a,4,5,6-hexahydro-8-methyl-1H-pyrazino [3,2,1-j,k]carbazol hydrochloride (pirlindole), a new antidepressant. Arzneimittelforschung. 1981;31(1):75-9. PubMed PMID: 7194096. 20: Ceccato A, Hubert P, de Tullio P, Liégeois JF, Stachow M, Géczy J, Crommen J. Simultaneous determination of pirlindole enantiomers and dehydropirlindole by chiral liquid chromatography. J Pharm Biomed Anal. 1998 Sep 1;17(6-7):1071-9. PubMed PMID: 9884197.