Amperozide

Amperozide is an atypical antipsychotic of the diphenylbutylpiperazine class which acts as an antagonist at the 5-HT2A receptor.[1] It does not block dopamine receptors as with most antipsychotic drugs,[2] but does inhibit dopamine release,[3][4] and alters the firing pattern of dopaminergic neurons.[5] It was investigated for the treatment of schizophrenia in humans,[6] but never adopted clinically. Its main use is instead in veterinary medicine, primarily in intensively farmed pigs, for decreasing aggression and stress and thereby increasing feeding and productivity.[7][8][9]

Amperozide
Clinical data
ATCvet code
Identifiers
IUPAC name
  • 4-[4,4-bis(4-fluorophenyl)butyl]-N-ethylpiperazine-1-carboxamide
CAS Number
PubChem CID
ChemSpider
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H29F2N3O
Molar mass401.502 g·mol−1
3D model (JSmol)
SMILES
  • CCNC(=O)N1CCN(CC1)CCCC(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F
InChI
  • InChI=1S/C23H29F2N3O/c1-2-26-23(29)28-16-14-27(15-17-28)13-3-4-22(18-5-9-20(24)10-6-18)19-7-11-21(25)12-8-19/h5-12,22H,2-4,13-17H2,1H3,(H,26,29) Y
  • Key:NNAIYOXJNVGUOM-UHFFFAOYSA-N Y
  (verify)

Synthesis

According to Arvid Carlsson, behavioural Stimulation in rat:[10]

Patents:[11][12]

The reaction of ethylisocyanate [109-90-0] (1) with N-benzylpiperazine (2) leads to the corresponding urea, CID:47103368 (3). Catalytic hydrogenation cleaves the benzyl protecting group giving N-ethylpiperazine-1-carboxamide [75529-72-5] (4). Alkylation of the unmasked nitrogen with 1,1'-(4-Chlorobutylidene)Bis(4-Fluorobenzene) [3312-04-7] (5) completed the synthesis of amperozide (6).

See also

Other agents in the diphenylbutylpiperazine group include:

References
  1. Svartengren J, Simonsson P (1990). "Receptor binding properties of amperozide". Pharmacology & Toxicology. 66 Suppl 1: 8–11. doi:10.1111/j.1600-0773.1990.tb01599.x. PMID 2154737.
  2. Meltzer HY, Zhang Y, Stockmeier CA (May 1992). "Effect of amperozide on rat cortical 5-HT2 and striatal and limbic dopamine D2 receptor occupancy: implications for antipsychotic action". European Journal of Pharmacology. 216 (1): 67–71. doi:10.1016/0014-2999(92)90210-u. PMID 1388121.
  3. Eriksson E (1990). "Amperozide, a putative anti-psychotic drug: uptake inhibition and release of dopamine in vitro in the rat brain". Life Sciences. 47 (23): 2111–7. doi:10.1016/0024-3205(90)90310-n. PMID 1979998.
  4. Yamamoto BK, Meltzer HY (October 1992). "The effect of the atypical antipsychotic drug, amperozide, on carrier-mediated striatal dopamine release measured in vivo". The Journal of Pharmacology and Experimental Therapeutics. 263 (1): 180–5. PMID 1403783.
  5. Grenhoff J, Tung CS, Ugedo L, Svensson TH (1990). "Effects of amperozide, a putative antipsychotic drug, on rat midbrain dopamine neurons recorded in vivo". Pharmacology & Toxicology. 66 Suppl 1: 29–33. doi:10.1111/j.1600-0773.1990.tb01603.x. PMID 2304893.
  6. Axelsson R, Nilsson A, Christensson E, Björk A (1991). "Effects of amperozide in schizophrenia. An open study of a potent 5-HT2 receptor antagonist". Psychopharmacology. 104 (3): 287–92. doi:10.1007/bf02246025. PMID 1924636.
  7. Kyriakis SC, Martinsson K, Olsson NG, Bjork A (1990). "Thin sow syndrome (TSS): the effect of amperozide". The British Veterinary Journal. 146 (5): 463–7. doi:10.1016/0007-1935(90)90036-3. PMID 2224491.
  8. Kyriakis SC, Olsson NG, Martinsson K, Björk AK (September 1991). "Observations on the action of amperozide: are there social influences on sow-litter productivity?". Research in Veterinary Science. 51 (2): 169–73. doi:10.1016/0034-5288(91)90008-C. PMID 1788479.
  9. Papp I, Waller C, Biro O (October 1996). "[Practical experiences in the therapy of postweaning edema disease in piglets]". Berliner und Munchener Tierarztliche Wochenschrift. 109 (10): 385–7. PMID 8999770.
  10. Waters, N., Pettersson, G., Carlsson, A., Svensson, K. (August 1989). "The putatively antipsychotic agent amperozide produces behavioural stimulation in the rat: A behavioural and biochemical characterization". Naunyn-Schmiedeberg’s Archives of Pharmacology. 340 (2). doi:10.1007/BF00168964. Retrieved 22 October 2022.
  11. DE2941880 idem Anders K. K. Bjork, Knut G. Olsson, Aina L. Abramo, Erik G. Christensson, U.S. Patent 4,447,433 (1984 to Ab Ferrosan).
  12. Anders K. K. Bjork, Knut G. Olsson, Aina L. Abramo, Erik G. Christensson, U.S. Patent 4,385,057 (1983 to Ab Ferrosan).
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