Panamesine

Panamesine (INN; developmental code name EMD-57455) is a sigma receptor antagonist that was under development by Merck as a potential antipsychotic for the treatment of schizophrenia in the 1990s but was never marketed.[1] It is a selective antagonist of both sigma receptor subtypes, the σ₁ and σ₂ receptors (IC₅₀ = 6 nM).[2] In addition, the major metabolite of the drug, EMD-59983, has high affinity for the sigma receptors (IC₅₀ = 24 nM) and the dopamine D₂ (IC₅₀ = 23 nM) and D₃ receptors, with potent antidopaminergic activity.[3][4][5] Panamesine reached phase II clinical trials for schizophrenia prior to the discontinuation of its development.[1]

Panamesine

Clinical data
Other names	EMD-57455
Pharmacokinetic data
Metabolites	EMD-59983
Identifiers
IUPAC name (5S)-5-[[4-(1,3-Benzodioxol-5-yl)-4-hydroxypiperidin-1-yl]methyl]-3-(4-methoxyphenyl)-1,3-oxazolidin-2-one
CAS Number	139225-22-2
PubChem CID	3047810
UNII	023D9E916L
ChEMBL	ChEMBL45686
CompTox Dashboard (EPA)	DTXSID00160971
Chemical and physical data
Formula	C23H26N2O6
Molar mass	426.469 g·mol^−1
3D model (JSmol)	Interactive image
SMILES COC1=CC=C(C=C1)N2C[C@@H](OC2=O)CN3CCC(CC3)(C4=CC5=C(C=C4)OCO5)O
InChI InChI=1S/C23H26N2O6/c1-28-18-5-3-17(4-6-18)25-14-19(31-22(25)26)13-24-10-8-23(27,9-11-24)16-2-7-20-21(12-16)30-15-29-20/h2-7,12,19,27H,8-11,13-15H2,1H3/t19-/m0/s1 Key:NINYZUDVKTUKIA-IBGZPJMESA-N

See also

• BMY-14802
• Eliprodil
• Rimcazole

References

1. "Panamesine". AdisInsight.
2. Guitart X, Codony X, Monroy X (2004). "Sigma receptors: biology and therapeutic potential". Psychopharmacology. 174 (3): 301–19. doi:10.1007/s00213-004-1920-9. PMID 15197533. S2CID 23606712.
3. Frieboes RM, Murck H, Wiedemann K, Holsboer F, Steiger A (1997). "Open clinical trial on the sigma ligand panamesine in patients with schizophrenia". Psychopharmacology. 132 (1): 82–8. doi:10.1007/s002130050323. PMID 9272763. S2CID 20525608.
4. Huber MT, Gotthardt U, Schreiber W, Krieg JC (1999). "Efficacy and safety of the sigma receptor ligand EMD 57445 (panamesine) in patients with schizophrenia: an open clinical trial". Pharmacopsychiatry. 32 (2): 68–72. doi:10.1055/s-2007-979194. PMID 10333165.
5. Gründer G, Müller MJ, Andreas J, Heydari N, Wetzel H, Schlösser R, Schlegel S, Nickel O, Eissner D, Benkert O (1999). "Occupancy of striatal D(2)-like dopamine receptors after treatment with the sigma ligand EMD 57445, a putative atypical antipsychotic". Psychopharmacology. 146 (1): 81–6. doi:10.1007/s002130051091. PMID 10485968. S2CID 7039752.