Panadiplon Explained

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 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]

Notes and References

  1. Tang AH, Franklin SR, Himes CS, Ho PM . Behavioral effects of U-78875, a quinoxalinone anxiolytic with potent benzodiazepine antagonist activity . The Journal of Pharmacology and Experimental Therapeutics . 259 . 1 . 248–54 . October 1991 . 1681085 .
  2. Ator NA, Griffiths RR . 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 . June 1999 . 10336537 .
  3. Rowlett JK, Woolverton WL . 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 . February 2001 . 11164687 . 10.1016/s0376-8716(00)00142-3 .
  4. Ulrich RG, Bacon JA, Branstetter DG, Cramer CT, Funk GM, Hunt CE, Petrella DK, Sun EL . Induction of a hepatic toxic syndrome in the Dutch-belted rabbit by a quinoxalinone anxiolytic . Toxicology . 98 . 1–3 . 187–98 . April 1995 . 7740546 . 10.1016/0300-483x(94)02951-p .
  5. Ulrich RG, Bacon JA, Brass EP, Cramer CT, Petrella DK, Sun EL . Metabolic, idiosyncratic toxicity of drugs: overview of the hepatic toxicity induced by the anxiolytic, panadiplon . Chemico-Biological Interactions . 134 . 3 . 251–70 . May 2001 . 11336974 . 10.1016/s0009-2797(01)00161-2 .
  6. Platt DM, Duggan A, Spealman RD, Cook JM, Li X, Yin W, Rowlett JK . 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 . May 2005 . 15650112 . 10.1124/jpet.104.080275 . 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 . 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 . November 2002 . 12388665 . 10.1124/jpet.102.036954 . 23880756 .

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Panadiplon".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.