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Milipertine

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Milipertine
Clinical data
Other namesMillipertine; WIN18935; WIN-18,935; Win-18935
Identifiers
  • 5,6-dimethoxy-3-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-2-methyl-1H-indole
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
Chemical and physical data
FormulaC24H31N3O3
Molar mass409.530 g·mol−1
3D model (JSmol)
  • CC1=C(C2=CC(=C(C=C2N1)OC)OC)CCN3CCN(CC3)C4=CC=CC=C4OC
  • InChI=1S/C24H31N3O3/c1-17-18(19-15-23(29-3)24(30-4)16-20(19)25-17)9-10-26-11-13-27(14-12-26)21-7-5-6-8-22(21)28-2/h5-8,15-16,25H,9-14H2,1-4H3
  • Key:XYAANYFFYIRFND-UHFFFAOYSA-N

Milipertine (INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name; developmental code name WIN-18935) is a drug described as an antipsychotic, neuroleptic, and tranquilizer which was under development for the treatment of schizophrenia but was never marketed.[1][2][3][4]

Structurally, it is a substituted tryptamine and a piperazinylethylindole.[5][6][7] The drug is closely structurally related to other "pertines" including alpertine, oxypertine, and solypertine, which are also tryptamines and piperazinylethylindoles.[5][6][8]

The related drug oxypertine shows high affinity for the serotonin 5-HT2 and dopamine D2 receptors (Ki = 8.6 nM and 30 nM, respectively) and is also known to act as a catecholamine depleting agent.[9][10] Oxypertine, milipertine, and solypertine all antagonize the behavioral effects of tryptamine, a serotonin receptor agonist, and apomorphine, a dopamine receptor agonist, in animals.[9][11] ortho-Methoxyphenylpiperazine (oMeOPP) has been said to be a metabolite of milipertine, as well as of oxypertine and several other drugs.[12][13]

Milipertine produced troublesome side effects in clinical studies including orthostatic hypotension, drowsiness, extrapyramidal symptoms, elevated liver enzymes, and weight loss.[14][15][4] The side effects of milipertine occurred too frequently and at doses well below those producing antipsychotic effects and its development was abandoned.[14][15][4]

Milipertine was first described in the scientific literature by 1968.[1]

References

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  1. ^ a b Elks, J. (2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer US. p. 825. ISBN 978-1-4757-2085-3. Retrieved 30 October 2024.
  2. ^ Negwer, M. (1994). Organic-chemical Drugs and Their Synonyms: (an International Survey). Akademie Verlag. p. 2306. ISBN 978-3-05-500156-7. Retrieved 30 October 2024.
  3. ^ Milne, G.W.A. (2002). Drugs: Synonyms and Properties. Wiley. p. 429. ISBN 978-0-566-08491-1. Retrieved 30 October 2024.
  4. ^ a b c Mielke DH, Gallant DM, Bishop MP (June 1973). "Milipertine: an early evaluation in severely ill schizophrenics". Curr Ther Res Clin Exp. 15 (6): 324–326. PMID 4197256.
  5. ^ a b Ellis, G.P.; Luscombe, D.K. (1996). Progress in Medicinal Chemistry. Elsevier Science. p. 219. ISBN 978-0-08-086281-1. Retrieved 30 October 2024. Pertines (class 7; Table 5.12) The pertines oxypertine, solypertine, milipertine, and alpertine are piperazinylethylindoles.
  6. ^ a b Lednicer, D.; Mitscher, L.A. (1980). The Organic Chemistry of Drug Synthesis, Volume 2. Organic Chemistry Series of Drug Synthesis. Wiley. pp. 341–343. ISBN 978-0-471-04392-8. Retrieved 30 October 2024.
  7. ^ Lednicer, D. (2009). Strategies for Organic Drug Synthesis and Design. Wiley. p. 390. ISBN 978-0-470-39959-0. Retrieved 30 October 2024.
  8. ^ Lajtha, A. (2013). Alterations of Metabolites in the Nervous System. Handbook of neurochemistry. Springer US. p. 335. ISBN 978-1-4757-6740-7. Retrieved 30 October 2024.
  9. ^ a b Megens AA, Kennis LE (1996). "Risperidone and related 5HT2/D2 antagonists: a new type of antipsychotic agent?". Prog Med Chem. Progress in Medicinal Chemistry. 33: 185–232. doi:10.1016/s0079-6468(08)70306-0. ISBN 978-0-444-82310-6. PMID 8776944.
  10. ^ Bak IJ, Hassler R, Kim JS (1969). "Differential monoamine depletion by oxypertine in nerve terminals. Granulated synaptic vesicles in relation to depletion of norepinephrine, dopamine and serotonin". Zeitschrift für Zellforschung und Mikroskopische Anatomie. 101 (3): 448–462. doi:10.1007/BF00335580. PMID 5362847. S2CID 32583722.
  11. ^ Niemegeers, Carlos J.E.; Janssen, Paul A.J. (1979). "Minireview A systematic study of the pharmacological activities of dopamine antagonists". Life Sciences. 24 (24). Elsevier BV: 2201–2216. doi:10.1016/0024-3205(79)90096-1. ISSN 0024-3205. PMID 388130.
  12. ^ Elliott S (2011). "Current awareness of piperazines: pharmacology and toxicology". Drug Test Anal. 3 (7–8): 430–438. doi:10.1002/dta.307. PMID 21744514. Furthermore, oMeOPP is a metabolite of some prescribed drugs: enciprazione, milipertine, urapidil, dropropizine and oxypertine.[1,47]
  13. ^ Caccia S, Notarnicola A, Fong MH, Benfenati E (January 1984). "Identification and quantitation of 1-arylpiperazines, metabolites resulting from side-chain cleavage of (4-substituted aryl-1-piperazinyl)alkyl heterocyclic derivatives in rat plasma and brain". J Chromatogr. 283: 211–221. doi:10.1016/s0021-9673(00)96256-3. PMID 6707118.
  14. ^ a b FDA Clinical Experience Abstracts. Food and Drug Administration. 1973. p. 1-PA15. Retrieved 30 October 2024.
  15. ^ a b Heinzelman, R.V. (1974). Annual Reports in Medicinal Chemistry. Academic Press. p. 3. ISBN 978-0-08-058353-2. Retrieved 30 October 2024.
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