Evaluation of antinociceptive activity of 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)cyclohexen-1-ol and its possible mechanisms of action in mice
Pain is one of the frequent reasons that one seeks for medical attention. Opiates and of non-steroidal anti-inflammatory drugs (NSAIDs) are the common treatments for various kinds of pain. However, the use of opiates often leads to undesirable effects such as constipation, nausea and even addicti...
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| Format: | Thesis |
| Language: | English |
| Published: |
2021
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/116177/ http://psasir.upm.edu.my/id/eprint/116177/1/116177.pdf |
| Summary: | Pain is one of the frequent reasons that one seeks for medical attention. Opiates
and of non-steroidal anti-inflammatory drugs (NSAIDs) are the common
treatments for various kinds of pain. However, the use of opiates often leads to
undesirable effects such as constipation, nausea and even addiction. Besides,
prolonged usage of NSAIDs tends to develop gastrointestinal and cardiovascular
dysfunctions in one’s body. Therefore, there’s an urgent need to accelerate the
drug discovery for new potent antinociceptive compound with equivalent painkilling
effect as the contemporary analgesics, but with minimal or no adverse
effects. The general objective of the present study was to determine the
antinociceptive activity of 2-benzoyl-6-(3-bromo-4-hydroxybenzylidene)
cyclohexen-1-ol (BBHC) at peripheral and central levels of nociception. Our
specific objectives were to study the antinociceptive property of BBHC against
peripheral inflammatory mediators, and also to investigate the participation of
BBHC in excitatory neurotransmission and central descending inhibitory
pathways (opioid and non-opioid pathways). The preliminary antinociceptive
activity of BBHC was screened with 3 antinociceptive tests, acetic acid-induced
abdominal constriction test, formalin-induced paw licking test and hot plate test.
Upon the confirmation of BBHC’s inhibitory effect against the chemically- and
thermally-induced nociception, BBHC was subjected to investigate for its
possible mechanisms of action towards peripherally-mediated inflammatory
mediators, excitatory neurotransmitters and a range of pain-modulating
receptors from descending inhibitory pathways. The findings from our present
study showed that BBHC significantly inhibited chemically- and thermallyinduced
pain from the 3 antinociceptive screening tests. BBHC had also reduced
pain caused by various inflammatory mediators and excitatory
neurotransmitters. The antinociception of BBHC was indicated to be associated
with descending inhibitory modulations, such as α2-adrenoreceptor, 5-HT1A
receptor, GABAA receptor, A1 adenosine receptor, D2-like dopaminergic receptor
and L-arginine-NO-cGMP-K+ channels pathway. Despite the significant
antinociceptive property of BBHC, it was confirmed that BBHC’s analgesic
activity is not related to muscle relaxation and sedation. BBHC’s LD50 was proven
to be greater than 2000 mg/kg which then classified BBHC as Category 5
according to the globally Harmonised System for classification of chemicals. As
conclusion, the present study has shown that BBHC-induced analgesia is
mediated by peripheral and central pain modulations of peripheral inflammatory
mediators, neurotransmitters and descending inhibitory pathways. |
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