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15. Positive allosteric modulators of the GABAB receptor: a new class of ligands with therapeutic potential for alcohol use disorder.

Author

Colombo, Giancarlo

Subjects
*GABA agonists, *BACLOFEN, *PHENOMENOLOGICAL biology, *BIOCHEMISTRY, *MICE, *ANIMAL behavior, *MOLECULAR structure, *ALCOHOLISM, *CELL receptors, *PHARMACODYNAMICS
Abstract

Background Positive allosteric modulators (PAMs) of the GABAB receptor constitute a new class of GABAB-receptor ligands. GABAB PAMs reproduce several pharmacological effects of the orthosteric GABAB receptor agonist, baclofen, although displaying a better safety profile. Aims This paper reviews the reducing or, frequently, even suppressing effects of all GABAB PAMs tested to date on multiple alcohol-related behaviours in laboratory rodents exposed to validated experimental models of human alcohol use disorder. Results Acute or repeated treatment with CGP7930, GS39783, BHF177, rac -BHFF, ADX71441, CMPPE, COR659, ASP8062, KK-92A, and ORM-27669 reduced excessive alcohol drinking, relapse- and binge-like drinking, operant alcohol self-administration, reinstatement of alcohol seeking, and alcohol-induced conditioned place preference in rats and mice. Conclusions These effects closely mirrored those of baclofen; notably, they were associated to remarkably lower levels of tolerance and toxicity. The recent transition of ASP8062 to clinical testing will soon prove whether these highly consistent preclinical data translate to AUD patients. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Impact of a quality programme on overindication of surgeries for endometriosis and cholecystectomies

Author

Conte de Oliveira, Mauro Dirlando, primary, Fernandes, Haggeas da Silveira, additional, Vasconcelos, Ana Luiz, additional, Russo, Fernanda Aparecida de Paula, additional, Malheiro, Daniel Tavares, additional, Colombo, Giancarlo, additional, Pelegrini, Paula, additional, Berwanger, Otavio, additional, Teich, Vanessa, additional, Marra, Alexandre, additional, Menezes, Fernando Gatti de, additional, Cendoroglo Neto, Miguel, additional, and Klajner, Sidney, additional

Published
2023
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24. Reducing effect of intragastrically administered saikosaponin A on alcohol and sucrose selfadministration in rats.

Author

Maccioni, Paola, Young-Won Chin, Corelli, Federico, Hak Cheol Kwon, and Colombo, Giancarlo

Subjects
SUCROSE, RATS, ALCOHOL, LABORATORY rats, HERBAL medicine
Abstract

Saikosaponin A (SSA) is an active ingredient of the Asian medicinal herb, Bupleurum falcatum L. When administered via the intraperitoneal (i.p.) route, SSA suppressed multiple addictive-like behaviours, including operant alcohol self-administration, in rodents. It is unknown whether these effects are retained after intragastric (i.g.) administration, a desirable prerequisite for a compound with therapeutic potential. To fill this gap, i.g. SSA (0, 50, and 100 mg/kg) was tested in Sardinian alcohol-preferring (sP) rats trained to lever-respond for oral alcohol. SSA reduced lever-responding and amount of self-administered alcohol. However, when compared to i.p. SSA, i.g. SSA resulted to be markedly less potent and effective, suggestive of reduced bioavailability after i.g. treatment. Finally, and in agreement with previous data on the suppressing effect of i.p. SSA on behaviours motivated by highly palatable foods, i.g. SSA (0, 50, and 100 mg/kg) reduced oral sucrose self-administration in a separate set of sP rats. [ABSTRACT FROM AUTHOR]

Published
2023
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30. Development of tolerance upon repeated administration with the GABAB receptor positive allosteric modulator, COR659, on alcohol drinking in rodents

Author

Lorrai, Irene, primary, Shankula, Chase, additional, Marquez Gaytan, Jorge, additional, Maccioni, Riccardo, additional, Lobina, Carla, additional, Maccioni, Paola, additional, Brizzi, Antonella, additional, Mugnaini, Claudia, additional, Gessa, Gian Luigi, additional, Sanna, Pietro Paolo, additional, Corelli, Federico, additional, and Colombo, Giancarlo, additional

Published
2022
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35. Analgesic effects of saikosaponin A in a rat model of chronic inflammatory pain.

Author

Lobina, Carla, Lee, Jung Hwan, Pel, Pisey, Chin, Young-Won, Kwon, Hak Cheol, and Colombo, Giancarlo

Subjects
CHRONIC pain, ANIMAL disease models, SALICYLIC acid, BUPLEURUM, HYPERALGESIA, EXPERIMENTAL arthritis
Abstract

Saikosaponin A (SSA) is the main active ingredient of roots of the East Asian medicinal plant, Bupleurum falcatum L. The present study was aimed at delving into the analgesic properties of SSA in a model of chronic inflammatory pain. To this end, rats were initially treated intraplantarly with complete Freund's adjuvant for induction of hyperalgesia. Twenty-four hours later, rats were acutely treated with SSA (0, 1 and 2 mg/kg, i.p.) and exposed to the Von Frey monofilament test or Randall–Selitto paw pressure test for assessment of mechanical hyperalgesia. Treatment with 2 mg/kg SSA had analgesic effects: the nocifensive reaction (paw withdrawal) occurred later and required application of the nociceptive stimulus at a stronger pressure. The analgesic effects of SSA were of magnitude comparable to that of the effects exerted by the reference compound, acetyl salicylic acid (100 mg/kg, i.p.). The well-described anti-inflammatory properties of SSA likely underlie its analgesic effects. [ABSTRACT FROM AUTHOR]

Published
2023
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37. Baclofen: clinical data

Author

Addolorato, Giovanni, Abenavoli, Ludovico, Leggio, Lorenzo, DeLorenzi, Giosuè, Ferrulli, Anna, Caputo, Fabio, Agabio, Roberta, Gessa, Gian Luigi, Colombo, Giancarlo, Gasbarrini, Giovanni, Parnham, Michael J., editor, Bruinvels, J., editor, Spanagel, Rainer, editor, and Mann, Karl F., editor

Published
2005
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38. Baclofen: preclinical data

Author

Carai, Mauro A.M., Agabio, Roberta, Addolorato, Giovanni, Gessa, Gian L., Colombo, Giancarlo, Parnham, Michael J., editor, Bruinvels, J., editor, Spanagel, Rainer, editor, and Mann, Karl F., editor

Published
2005
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41. Prevalence and influence of cys407* Grm2 mutation in Hannover-derived Wistar rats: mGlu2 receptor loss links to alcohol intake, risk taking and emotional behaviour

Author

Wood, Christian M., Nicolas, Celine S., Choi, Sun-Lim, Roman, Erika, Nylander, Ingrid, Fernandez-Teruel, Alberto, Kiianmaa, Kalervo, Bienkowski, Przemyslaw, de Jong, Trynke R., Colombo, Giancarlo, Chastagnier, Denis, Wafford, Keith A., Collingridge, Graham L., Wildt, Sheryl J., Conway-Campbell, Becky L., Robinson, Emma S.J., and Lodge, David

Published
2017
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