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Antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models.

Hajhashemi V, Dehdashti Kh - Res Pharm Sci (2014 Sep-Oct)

Bottom Line: Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group.Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively.Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

ABSTRACT
Glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. It has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. Therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Male Swiss mice (25-30 g) were used in this study. Acetic acid-induced writhing, formalin test and hot plate method were used to assess the antinociceptive effect of clavulanic acid. Morphine (30 mg/kg, s.c.) was administered to the mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. To develop morphine dependence, morphine sulfate (50, 50 and 75 mg/kg) was injected at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group. Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively. Clavulanic acid was not able to show any antinociception in hot plate model and could not prevent development of tolerance and dependence to morphine. Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

No MeSH data available.


Related in: MedlinePlus

Effect of i.p. injection of clavulanic acid on acetic acid-induced writhing test in mice (n=6). Clavulanic acid (10, 20 and 40 mg/kg), indomethacin (10 mg/kg) and the vehicle were administered 30 min prior to acetic acid (1%) injection (i.p.) and the number of abdominal contractions was counted for each mouse for a period of 10 min starting 10 min after acetic acid injection. The values represent the mean of abdominal twitches ± SEM. *p<0.05; ***p<0.001 compared with control group.
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Figure 1: Effect of i.p. injection of clavulanic acid on acetic acid-induced writhing test in mice (n=6). Clavulanic acid (10, 20 and 40 mg/kg), indomethacin (10 mg/kg) and the vehicle were administered 30 min prior to acetic acid (1%) injection (i.p.) and the number of abdominal contractions was counted for each mouse for a period of 10 min starting 10 min after acetic acid injection. The values represent the mean of abdominal twitches ± SEM. *p<0.05; ***p<0.001 compared with control group.

Mentions: In acetic acid-induced writhing test, clavulanic acid at doses of 10 and 20 mg/kg significantly (p<0.05) inhibited acetic acid-induced abdominal constrictions and a highly significant decrease was seen at dose of 40 mg/kg (p<0.001). In this test indomethacin, as the reference drug at a dose of 10 mg/kg produced about 81.8% reduction of writhes (Fig. 1).


Antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models.

Hajhashemi V, Dehdashti Kh - Res Pharm Sci (2014 Sep-Oct)

Effect of i.p. injection of clavulanic acid on acetic acid-induced writhing test in mice (n=6). Clavulanic acid (10, 20 and 40 mg/kg), indomethacin (10 mg/kg) and the vehicle were administered 30 min prior to acetic acid (1%) injection (i.p.) and the number of abdominal contractions was counted for each mouse for a period of 10 min starting 10 min after acetic acid injection. The values represent the mean of abdominal twitches ± SEM. *p<0.05; ***p<0.001 compared with control group.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317999&req=5

Figure 1: Effect of i.p. injection of clavulanic acid on acetic acid-induced writhing test in mice (n=6). Clavulanic acid (10, 20 and 40 mg/kg), indomethacin (10 mg/kg) and the vehicle were administered 30 min prior to acetic acid (1%) injection (i.p.) and the number of abdominal contractions was counted for each mouse for a period of 10 min starting 10 min after acetic acid injection. The values represent the mean of abdominal twitches ± SEM. *p<0.05; ***p<0.001 compared with control group.
Mentions: In acetic acid-induced writhing test, clavulanic acid at doses of 10 and 20 mg/kg significantly (p<0.05) inhibited acetic acid-induced abdominal constrictions and a highly significant decrease was seen at dose of 40 mg/kg (p<0.001). In this test indomethacin, as the reference drug at a dose of 10 mg/kg produced about 81.8% reduction of writhes (Fig. 1).

Bottom Line: Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group.Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively.Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

ABSTRACT
Glutamate has a key role in pain perception and also development of tolerance and dependence to morphine. It has been reported that clavulanic acid affects glutamatergic transmission via activation of glutamate transporter. Therefore the present study was aimed to evaluate the possible antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Male Swiss mice (25-30 g) were used in this study. Acetic acid-induced writhing, formalin test and hot plate method were used to assess the antinociceptive effect of clavulanic acid. Morphine (30 mg/kg, s.c.) was administered to the mice two times a day (8 AM and 4 PM) for 3 days in order to produce tolerance. To develop morphine dependence, morphine sulfate (50, 50 and 75 mg/kg) was injected at 8 and 12 AM and 16 PM respectively and for 3 consecutive days. Naloxone (5 mg/kg, i.p) was used to induce morphine withdrawal syndrome and the number of jumps and presence of ptosis, piloerection, tremor, sniffing and diarrhea were recorded and compared with control group. Clavulanic acid at doses of 10, 20 and 40 mg/kg inhibited abdominal constriction and licking behavior of acetic acid and formalin-induced pain respectively. Clavulanic acid was not able to show any antinociception in hot plate model and could not prevent development of tolerance and dependence to morphine. Clavulanic acid has considerable antinociceptive activity and further studies are needed to clarify its exact mechanism.

No MeSH data available.


Related in: MedlinePlus