Milipertine

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Milipertine
Milipertine.svg
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
Formula C24H31N3O3
Molar mass 409.530 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 (INN Tooltip International Nonproprietary Name, USAN Tooltip 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]

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<span class="mw-page-title-main">Levofenfluramine</span> Non-marketed drug of the amphetamine class

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<span class="mw-page-title-main">Enciprazine</span> Chemical compound

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<span class="mw-page-title-main">Alpertine</span> Abandoned antipsychotic

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<span class="mw-page-title-main">Solypertine</span> Abandoned sympatholytic drug

Solypertine, also known as solypertine tartrate in the case of the tartrate salt, is a drug described as an antiadrenergic and as also potentially possessing neuroleptic properties which was never marketed.

<i>ortho</i>-Methoxyphenylpiperazine Serotonergic drug

ortho-Methoxyphenylpiperazine (oMeOPP), also known as 2-methoxyphenylpiperazine (2-MeOPP), is a phenylpiperazine derivative which is known to act as a serotonergic agent. Along with various other phenylpiperazines, like benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP), oMeOPP has been found in illicit drug samples.

References

  1. 1 2 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 GW (2002). Drugs: Synonyms and Properties. Wiley. p. 429. ISBN   978-0-566-08491-1 . Retrieved 30 October 2024.
  4. 1 2 3 Mielke DH, Gallant DM, Bishop MP (June 1973). "Milipertine: an early evaluation in severely ill schizophrenics". Current Therapeutic Research, Clinical and Experimental. 15 (6): 324–326. PMID   4197256.
  5. 1 2 Ellis GP, Luscombe DK (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. 1 2 Lednicer D, Mitscher LA (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. 1 2 Megens AA, Kennis LE (1996). Risperidone and related 5HT2/D2 antagonists: a new type of antipsychotic agent?. Progress in Medicinal Chemistry. Vol. 33. pp. 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 Fur Zellforschung und Mikroskopische Anatomie. 101 (3): 448–462. doi:10.1007/BF00335580. PMID   5362847. S2CID   32583722.
  11. ↑ Niemegeers CJ, Janssen PA (June 1979). "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. PMID   388130.
  12. ↑ Elliott S (2011). "Current awareness of piperazines: pharmacology and toxicology". Drug Testing and Analysis. 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". Journal of Chromatography. 283: 211–221. doi:10.1016/s0021-9673(00)96256-3. PMID   6707118.
  14. 1 2 FDA Clinical Experience Abstracts. Food and Drug Administration. 1973. p. 1-PA15. Retrieved 30 October 2024.
  15. 1 2 Heinzelman RV (1974). Annual Reports in Medicinal Chemistry. Academic Press. p. 3. ISBN   978-0-08-058353-2 . Retrieved 30 October 2024.
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