HYPOTHERMIC ACTIVITY OF ACETAMINOPHEN; INVOLVEMENT OF GABAA RECEPTOR, THEORETICAL AND EXPERIMENTAL STUDIES

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AHANGAR NEMATOLLAH; ESAM ZOHREH; BEKHRADNIA AHMADREZA; EBRAHIMZADEH MOHAMMAD ALI

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Journal Paper

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Journal: Iranian Journal of Basic Medical Sciences Year:2016 | Volume:19 | Issue:5 Page(s): 470-475

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Title

HYPOTHERMIC ACTIVITY OF ACETAMINOPHEN; INVOLVEMENT OF GABAA RECEPTOR, THEORETICAL AND EXPERIMENTAL STUDIES

Author(s)

AHANGAR NEMATOLLAH | ESAM ZOHREH | BEKHRADNIA AHMADREZA | EBRAHIMZADEH MOHAMMAD ALI | Issue Writer Certificate

Keywords

ABINITIO STUDY

ACETAMINOPHEN

BENZODIAZEPINE RECEPTOR

HYPOTHERMIA

GABAA

Abstract

Objective (s): The mechanism of HYPOTHERMIA action of ACETAMINOPHEN (APAP) remains unclear even 125 years after its synthesis. ACETAMINOPHEN produces HYPOTHERMIA. The mechanism of this reduction in core body temperature is not clear but evidence shows that it is not dependent on opioid and cannabinoid receptors. Because of strong documents about the roles of GABA and BENZODIAZEPINE RECEPTORs in hypothemic activity of some drugs such as diazepam, we determined if these receptors also contributes to the hypothermic effect of APAP.Materials and Methods: Diazepam (5 mg/kg, IP) was used for induction of HYPOTHERMIA. Flumazenil (10 mg/kg, IP) or picrotoxin (2 mg/kg, IP) used for reversal of this effect. Rats injected with APAP (100, 200 or 300 mg/kg, IP). Baseline temperature measurements were taken with a digital thermometer via rectum. To evaluate the structural correlation between APAP and BENZODIAZEPINE RECEPTOR ligands, numerous models are selected and studied at HF/6-31G* level of theory. Relative energies, enthalpies and Gibbs free energies were calculated for all selected drugs.Results: Diazepam induced HYPOTHERMIA was reversed by flumazenil or picrotoxin. Rats injected with APAP displayed dose- and time-related HYPOTHERMIA. For combined administration, the hypothermic effect of APAP (200 mg/kg) was strongly reduced by pretreatment with picrotoxin or flumazenil P<0.0001and P<0.01, respectively. Selective structural data, bond length, dihedral angles, and related distance in pharmacophore of APAP and BZDR models were the same. Some significant structural analogues were obtained between these drugs.Conclusion: Results suggest hypothermic action of ACETAMINOPHEN may be mediate by its effect at GABAA BENZODIAZEPINE RECEPTOR.

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APA: Copy

AHANGAR, NEMATOLLAH, ESAM, ZOHREH, BEKHRADNIA, AHMADREZA, & EBRAHIMZADEH, MOHAMMAD ALI. (2016). HYPOTHERMIC ACTIVITY OF ACETAMINOPHEN; INVOLVEMENT OF GABAA RECEPTOR, THEORETICAL AND EXPERIMENTAL STUDIES. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, 19(5), 470-475. SID. https://sid.ir/paper/696187/en

Vancouver: Copy

AHANGAR NEMATOLLAH, ESAM ZOHREH, BEKHRADNIA AHMADREZA, EBRAHIMZADEH MOHAMMAD ALI. HYPOTHERMIC ACTIVITY OF ACETAMINOPHEN; INVOLVEMENT OF GABAA RECEPTOR, THEORETICAL AND EXPERIMENTAL STUDIES. IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES[Internet]. 2016;19(5):470-475. Available from: https://sid.ir/paper/696187/en

IEEE: Copy

NEMATOLLAH AHANGAR, ZOHREH ESAM, AHMADREZA BEKHRADNIA, and MOHAMMAD ALI EBRAHIMZADEH, “HYPOTHERMIC ACTIVITY OF ACETAMINOPHEN; INVOLVEMENT OF GABAA RECEPTOR, THEORETICAL AND EXPERIMENTAL STUDIES,” IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES, vol. 19, no. 5, pp. 470–475, 2016, [Online]. Available: https://sid.ir/paper/696187/en

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