Article · Wikipedia archive · Last revised Jun 24, 2026

EXP-561

EXP-561 is an investigational drug that acts as an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine. It was developed in the 1960s by Du Pont and was suggested as a potential antidepressant but failed in trials and was never marketed.

Last revised
Jun 24, 2026
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≈ 2 min
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543 w
Citations
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Wikipedia ↗
EXP-561
Clinical data
Routes of
administration		Oral
ATC code
  • none
Legal status
Legal status
  • In general: uncontrolled
Identifiers
  • 4-phenylbicyclo[2.2.2]octan-1-amine
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H19N
Molar mass201.313 g·mol−1
3D model (JSmol)
  • NC12CCC(CC1)(CC2)C3=CC=CC=C3
  • InChI=1S/C14H19N.ClH/c15-14-9-6-13(7-10-14,8-11-14)12-4-2-1-3-5-12;/h1-5H,6-11,15H2;1H
  • Key:LTHJBDQSFIGMAZ-UHFFFAOYSA-N

EXP-5611 is an investigational drug that acts as an inhibitor of the reuptake of serotonin, dopamine, and norepinephrine.2345 It was developed in the 1960s by Du Pont6 and was suggested as a potential antidepressant but failed in trials7 and was never marketed.58910

SAR simplification in the molecular structure leads to a compound called 4-Phenylcyclohexylamine [19992-45-1].11 This is produced by reduction of the oxime of a commercially available compound that is called 4-phenylcyclohexanone. It is noteworthy to point out that this precursor might forseeably share a dual use in the synthesis of danavorexton.

In one method of synthesis, EXP-561 is made from a chemical that is called 3-carboethoxy-6-phenyl-2-pyrone [6465-14-1]. The disadvantage of this method is that it needed to be heated with ethylene in benzene solvent at 200C for 16 hours at 1000 atmospheres, so a suitable pressure vessel was needed. Although, alternative protocols were addressed that sought to circumvent this limitation.12 However, this much pressure seemed excessive and a more recent patent only employed 75 bar pressure.

See also

See also

References

References

  1. US 3362878, Snyder JA, "Pharmaceutical compositions and methods utilizing substituted bicyclo[2.2.2]-octanes", issued 9 January 1968, assigned to EIDP Inc. 
  2. Fuller RW, Snoddy HD, Perry KW (November 1976). "Inhibition of amine uptake by 4-phenyl-bicyclo(2,2,2)octan-1-amine hydrochloride monohydrate (EXP 561) in rats". biochemical Pharmacology. 25 (21): 2409–2410. doi:10.1016/0006-2952(76)90039-3. PMID 999731.
  3. BK K (December 1976). "Molecular geometry of inhibitors of the uptake of catecholamines and serotonin in synaptosomal preparations of rat brain". The Journal of Pharmacology and Experimental Therapeutics. 199 (3): 649–661. doi:10.1016/S0022-3565(25)30726-3. PMID 994022.
  4. Wong DT, Molloy BB, Bymaster FP (January 1977). "Blockade of monoamine uptake by 1-amino-4-phenylbicyclo(2,2,2)octane (EXP 561) in rat brain and heart". Neuropharmacology. 16 (1): 11–15. doi:10.1016/0028-3908(77)90040-5. PMID 834358. S2CID 44365500.
  5. Maj J, Skuza G, Sowińska H, Nowak G (1987). "Pharmacological properties of EXP 561, a potential antidepressant drug". Journal of Neural Transmission. 70 (1–2): 81–97. doi:10.1007/BF01252511. PMID 2822850. S2CID 23469131.
  6. US 3308160, Snyder JA, "4-Phenylbicyclo[2.2.2]octane-1-amines and salts thereof", issued 7 March 1967, assigned to EIDP Inc. 
  7. Davis JM (1970). "Theories of biological etiology of affective disorders". In Pfeiffer CC, Smythies JR (eds.). International Review of Neurobiology. Vol. 12. pp. 145–175. doi:10.1016/s0074-7742(08)60060-4. ISBN 978-0-12-366812-7. PMID 4918142.
  8. Lehmann HE, Ban TA, Debow SL (June 1967). "A clinical-pharmacological study with EXP 561". Current Therapeutic Research, Clinical and Experimental. 9 (6): 306–308. PMID 4963065.
  9. Gershon S, Hekimian LJ, Floyd A (February 1968). "Non-correlation of preclinical-clinical evaluation of a prosposed anti-depressant 4-phenyl-bicyclo(2,2,2)octan-1-amine hydrochloride monohydrate (EXP 561)". Arzneimittel-Forschung. 18 (2): 243–245. PMID 5695389.
  10. Ross SB, Kelder D (May 1979). "Inhibition of 3H-dopamine accumulation in reserpinized and normal rat striatum". Acta Pharmacologica et Toxicologica. 44 (5): 329–335. doi:10.1111/j.1600-0773.1979.tb02339.x. PMID 474143.
  11. Carenini G, Carissimi M, D'Ambrosio R, Grumelli E, Milla E, Ravenna F (1973). "[Phenylcyclohexylamine and derivatives. IV. Salts of trans-4-phenylcyclohexylamine with -substituted 4-diphenyl- and 4-cyclohexylphenyl acetic acids and their pharmacological activity]". Il Farmaco; Edizione Scientifica. 28 (4): 265–277. PMID 4698884.
  12. Chapman, N. B., Sotheeswaran, S., Toyne, K. J. (April 1970). "Preparation of 4-substituted 1-methoxycarbonylbicyclo[2.2.2]octanes, 4-substituted 1-phenylbicyclo[2.2.2]octanes, 4-substituted 1-p-nitrophenylbicyclo[2.2.2]octanes and 1,4-disubstituted bicyclo[2.2.2]octanes". The Journal of Organic Chemistry. 35 (4): 917–923. doi:10.1021/jo00829a010.