Pharmacological profile of three different γ-butyrolactone derivatives in mice
More details
Hide details
Department of Pharmacodynamics, Jagiellonian University Medical College, Medyczna 9, 30- 688 Cracow, Poland
Corresponding author
Kinga Sałat   

Department of Pharmacodynamics, Medical College, Jagiellonian University, Medyczna 9, 30-688 Cracow, Poland.
J Pre Clin Clin Res. 2010;4(1):14-18
The paper presents the pharmacological profi le of the analgesic activity of 3 derivatives of γ-butyrolactone (GBL), marked with the symbols: LMOR, LHEL and L8. In view of the available data indicating potent antinociceptive activity of some GBL, analgesic activity of these compounds was investigated in a few screening models, namely the hot plate, writhing and capsaicin tests. Moreover, spontaneous locomotor activity, local anesthetic activity in modifi ed tail immersion test and acute toxicity were also evaluated. The results of the experiments confirm antinociceptive activity in a vast range of rodent models of pain, especially pain induced by thermal (the hot plate and modified tail immersion tests) or chemical (phenylbenzoquinone but not capsaicin) stimuli.
Le Bars D, Gozariu M, Cadden SW: Animal models of nociception. Pharmacol Rev 2001, 53, 597-652.
Omoigui S: The biochemical origin of pain: the origin of all pain is infl ammation and the infl ammatory response. Part 2 of 3 - infl amatory profi le of pain syndromes. Med Hypotheses 2007, 69, 1169-1178.
Przewłocki R, Przewłocka B: Opioids in chronic pain. Eur J Pharmacol 2001, 429, 79-91.
Bohlega S, Alsaadi T, Amir A, Hosny H, Karawagh AM, Moulin D, Riachi N, Salti A, Shelbaya S: Guidelines for the pharmacological treatment of peripheral neuropathic pain: expert panel recommendations for the middle East region. J Int Med Res 2010, 38, 295-317.
McCleane G: Antidepressants as analgesics. CNS Drugs 2008, 22, 139-156.
Sałat K, Filipek B, Więckowski K, Malawska B: Analgesic activity of 3-mono-substituted derivatives of dihydrofuran-2-one in experimental rodent models of pain. Pharmacol Rep 2009, 61, 807-818.
Vonvoigtlander PF, Lewis RA, Neff GL: Kappa opioid analgesia isdependent on serotonergic mechanisms. J Pharmacol Exp Ther 1984, 231, 270-281.
Ettinger AB, Argoff CE: Use of antiepileptic drugs for nonepileptic conditions: psychiatric disorders and chronic pain. Neurotherapeutics 2007, 4, 75-83.
Paluchowska M, Mokrosz MJ, Charakchieva-Minol S, Duszyńska B, Kozioł A, Wesołowska A, Stachowicz K, Chojnacka-Wojcik E: Novel 4-alkyl-1-arylpiperazines and 1,2,3,4-tetrahydroisoquinolines containing diphenylmethylamino or diphenylmethoxy fragment with diff erentiated 5-HT1A/5-HT2A/D2 receptor activity. Pol J Pharmacol 2003, 55, 543-552.
Hunter JC, Gogas KR, Hedley LR, Jacobson LO, Kassotakis L, Thompson J, Fontana DJ: The eff ect of novel anti-epileptic drugs in rat experimental models of acute and chronic pain. Eur J Pharmacol 1997, 324, 153-160.
Laughlin TM, Tram KV, Wilcox GL, Birnbaum AK: Comparison of antiepileptic drugs tiagabine, lamotrigine, and gabapentin in mouse models of acute, prolonged and chronic nociception. J Pharmacol Exp Ther 2002, 302, 1168-1175.
Malawska B, Gobaille S: Synthesis, physicochemical and pharmacological properties of new N-substituted amides of α- piperazine-γ-hydroxybutyric acid. Pharmazie 1995, 50, 390–393.
Malawska B, Kulig K, Gajda J, Szczeblewski D, Musiał A, Więckowski K, Stables JP: Design, synthesis and pharmacological evaluation of α- substituted N-benzylamides of γ-hydroxybutyric acid with potential GABA-ergic activity. Part 6. Search for new anticonvulsant compounds. Acta Polon Pharm -Drug Research 2007, 64, 127-137.
Malawska B, Kulig K, Śpiewak A, Stables JP: Investigation into new anticonvulsant derivatives of α-substituted N-benzylamides of γ-hydroxy- and γ-acetoxybutyric acid. Part 5. Search for new anticonvulsant compounds. Bioorg Med Chem 2004, 12, 625-632.
Sahebgharani M, Hossein-Abad A, Zarrindast MR: On the mechanism of carbamazepin-induced antinociception in the formalin test. Intern J Neurosci 2006, 116, 1097-1113.
Waszkielewicz A, Bojarski J: γ-Hydroxybutyric acid (GHB) and its chemical modifi cations: a review of the GHBergic system. Pol J Pharmacol 2004, 56, 43-49.
Canney DJ, Lu HF, McKeon AC, Yoon KW, Xu K, Holland KD, Rothman SM, Ferrendelli JA, Covey DF: Structure-activity studies of fl uoroalkylsubstituted γ-butyrolactone and γ-thiobutyrolactone modulators of GABAA receptor function. Bioorg Med Chem 1998, 6, 43-55.
Hadri AE, Abouabdellah A, Thomet U, Bauer R, Furtmuller R, Sigel E, Sieghart W, Dodd RH: N-Substituted 4-amino-3,3-diphenyl-2(3H)- furanones: New positive allosteric modulators of the GABAA receptor sharing electrophysiological properties with the anticonvulsant loreclezole. J Med Chem 2002, 45, 2824-2831.
Williams KL, Tucker JB, White G, Weiss DS, Ferrendelli JA, Covey DF, Krause JE, Rothman SM: Lactone modulation of the γ-aminobutyric acid A receptor: Evidence for a positive modulatory site. Mol Pharmacol 1997, 52, 114-119.
Obniska J, Kamiński K, Tatarczyńska E: Impact of aromatic substitution on the anticonvulsant activity of new N-(4-arylpiperazin-1-yl)-alkyl- 2-azaspiro[4.5]decane-1,3-dione derivatives. Pharmacol Rep 2006, 58, 207-214.
Rohet F, Rubat C, Coudert P, Couquelet J: Synthesis and analgesic eff ects of 3-substituted 4,6-diarylpyridazine derivatives of the arylpiperazine class. Bioorg Med Chem 1997, 5, 655-659.
Eddy N, Leimbach D: Synthetic analgesics. II. Dithienylbutenyl – and dithienylbutylamines. J Pharmacol Exp Ther 1953, 107, 385-393.
Vogel HG, Vogel WH: Drug discovery and evaluation. Pharmacological assays. Springer-Verlag Inc., New York, 1997.
Hendershot LC, Forsaith J: Antagonism of the frequency of phenylbenzoquinone induced writhing in the mouse by weak analgesics and non-analgesics. J Pharmacol Exp Ther 1959, 125, 237-240.
Santos ARS, Gadotti VM, Oliveira GL, Tibola D, Paszcuk AF, Neto A, Spindola HM, Souza MM, Rodrigues ALS, Calixto JB: Mechanism involved in the antinociception caused by agmatine in mice. Neuropharmacology 2005, 48, 1021-1034.
Erenmemisoglu A, Suer C, Temocin M: Has nicotine a local anaesthetic action? J Bas Clin Physiol Pharmacol 1994, 5, 125-131.
Litchfi eld JT, Wilcoxon E: A simplifi ed method of evaluating dose-eff ect experiments. J Pharmacol Exp Ther 1949, 96, 99-113.
Hough LB, Nalwalk JW, Stadel R, Timmerman H, Leurs R, Paria BC, Wang X, Dey SK: Inhibition of improgan antinociception by the cannabinoid CB1 antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)- 1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A): Lack of obligatory role for endocannabinoids acting at CB1 receptors. J Pharmacol Exp Ther 2002, 303, 314-322.
Bishop B: Pain: its physiology and rationale for management. Part III. Consequences of current concepts of pain mechanisms related to pain management. Phys Ther 1980, 60, 24-37.
Jasmin L. Wu MV, Ohara PT: GABA puts a stop to pain. Curr Drugs Targets CNS Neurol Disord 2004, 3, 487-505.
Mohler H, Crestani F, Rudolph U: GABAA-receptor subtypes: a new pharmacology. Curr Opin Pharmacol 2001, 1, 22-25.
Adcock JJ: TRPV1 receptors in sensitization of cough and pain refl exes. Pulm Pharmacol Ther 2009, 22, 65-70.
Calixto JB, Kassuya CAL, Andre E, Ferreira J: Contribution of natural products to the discovery of the transient receptor potential (TRP) channels family and their functions. Pharmacol Ther 2005, 106, 179- 208.
Cui M, Honore P, Zhong C, Gauvin D, Mikusa J, Hernandez G, Chandran P, Gomtsyan A, Brown B, Bayburt EK, Marsh K, Bianchi B,. McDonald H, Niforatos W, Neelands TR, Moreland RB, Decker MW, Lee CH, Sullivan JP, Faltynek CR: TRPV1 receptors in the CNS play a key role in broad-spectrum analgesia of TRPV1 antagonist. J Neurosci 2006, 26, 9385-9393.
Planells-Cases R, Garcia-Sanz N, Morenilla-Palao C, Ferrer-Montiel A: Functional aspects and the mechanisms of TRPV1 involvement in neurogenic infl ammation that leads to thermal hyperalgesia. Eur J Physiol 2005, 451, 151-159.
Journals System - logo
Scroll to top