Panadiplon

Panadiplon (U-78875) is an anxiolytic drug with a novel chemical structure that is not closely related to other drugs of this type. It has a similar pharmacological profile to the benzodiazepine family of drugs, but with mainly anxiolytic properties and relatively little sedative or amnestic effect, and so is classified as a nonbenzodiazepine anxiolytic.[1]

Panadiplon
Clinical data
ATC code
  • none
Legal status
Legal status
Identifiers
IUPAC name
  • 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5 -propan-2-ylimidazo[5,1-c]quinoxalin-4-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H17N5O2
Molar mass335.367 g·mol−1
3D model (JSmol)
SMILES
  • O=C4N(c5ccccc5n3cnc(c1nc(on1)C2CC2)c34)C(C)C
InChI
  • InChI=1S/C18H17N5O2/c1-10(2)23-13-6-4-3-5-12(13)22-9-19-14(15(22)18(23)24)16-20-17(25-21-16)11-7-8-11/h3-6,9-11H,7-8H2,1-2H3 Y
  • Key:ZGEGOFCLSWVVKG-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Panadiplon acts as a high-affinity GABAA receptor partial agonist,[2][3] but despite showing a useful effects profile of a potent anxiolytic with little sedative effects, panadiplon was discontinued from clinical development for use in humans after showing evidence of liver damage in both animals and human trials.[4][5] Panadiplon however continues to be used in animal research, mainly as a subtype-selective reference drug to compare other GABAA agonists against.[6][7]

References
  1. Tang AH, Franklin SR, Himes CS, Ho PM (October 1991). "Behavioral effects of U-78875, a quinoxalinone anxiolytic with potent benzodiazepine antagonist activity". The Journal of Pharmacology and Experimental Therapeutics. 259 (1): 248–54. PMID 1681085.
  2. Ator NA, Griffiths RR (June 1999). "Drug discrimination analysis of partial agonists at the benzodiazepine site. I. Differential effects of U-78875 across training conditions in baboons and rats". The Journal of Pharmacology and Experimental Therapeutics. 289 (3): 1434–46. PMID 10336537.
  3. Rowlett JK, Woolverton WL (February 2001). "Discriminative stimulus effects of panadiplon (U-78875), a partial agonist at the benzodiazepine site, in pentobarbital-trained rhesus monkeys". Drug and Alcohol Dependence. 61 (3): 229–36. doi:10.1016/s0376-8716(00)00142-3. PMID 11164687.
  4. Ulrich RG, Bacon JA, Branstetter DG, Cramer CT, Funk GM, Hunt CE, Petrella DK, Sun EL (April 1995). "Induction of a hepatic toxic syndrome in the Dutch-belted rabbit by a quinoxalinone anxiolytic". Toxicology. 98 (1–3): 187–98. doi:10.1016/0300-483x(94)02951-p. PMID 7740546.
  5. Ulrich RG, Bacon JA, Brass EP, Cramer CT, Petrella DK, Sun EL (May 2001). "Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity induced by the anxiolytic, panadiplon". Chemico-Biological Interactions. 134 (3): 251–70. doi:10.1016/s0009-2797(01)00161-2. PMID 11336974.
  6. Platt DM, Duggan A, Spealman RD, Cook JM, Li X, Yin W, Rowlett JK (May 2005). "Contribution of alpha 1GABAA and alpha 5GABAA receptor subtypes to the discriminative stimulus effects of ethanol in squirrel monkeys". The Journal of Pharmacology and Experimental Therapeutics. 313 (2): 658–67. doi:10.1124/jpet.104.080275. PMID 15650112. S2CID 97681615.
  7. Dubinsky B, Vaidya AH, Rosenthal DI, Hochman C, Crooke JJ, DeLuca S, DeVine A, Cheo-Isaacs CT, Carter AR, Jordan AD, Reitz AB, Shank RP (November 2002). "5-ethoxymethyl-7-fluoro-3-oxo-1,2,3,5-tetrahydrobenzo[4,5]imidazo[1,2a]pyridine-4-N-(2-fluorophenyl)carboxamide (RWJ-51204), a new nonbenzodiazepine anxiolytic". The Journal of Pharmacology and Experimental Therapeutics. 303 (2): 777–90. doi:10.1124/jpet.102.036954. PMID 12388665. S2CID 23880756.
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