Panadiplon

Panadiplon

Clinical data
ATC code	none
Legal status
Legal status	See Hepatotoxic
Identifiers
IUPAC name 3-(5-cyclopropyl-1,2,4-oxadiazol-3-yl)-5 -propan-2-ylimidazo[5,1-c]quinoxalin-4-one
CAS Number	124423-84-3  N
PubChem CID	3033821
ChemSpider	2298411  Y
UNII	V4PW0S7ZP7
KEGG	D05346  Y
ChEMBL	ChEMBL279867  Y
CompTox Dashboard (EPA)	DTXSID40869698
Chemical and physical data
Formula	C18H17N5O2
Molar mass	335.367 g·mol−1
3D model (JSmol)	Interactive image
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 (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 acts as a high-affinity GABA_A 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 GABA_A 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.