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Analgesic and Toxicity Studies of Aminoacetylenic Isoindoline-1,3-dione Derivatives.

Shakir R, Muhi-Eldeen ZA, Matalka KZ, Qinna NA - ISRN Pharmacol (2012)

Bottom Line: We have developed a series of aminoacetylenic isoindoline-1,3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines.Moreover, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic and anti-inflammatory activity compared to indomethacin as a positive control.The results indicate that ZM4 and ZM5 possess potential analgesic activity while being preliminarily safe and have minimal ulcerogenic activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, Petra University, P.O. Box 961343, Amman 11196, Jordan.

ABSTRACT
We have developed a series of aminoacetylenic isoindoline-1,3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines. In the present study and due to efficacy reasons, we are exploring only two of these compounds, namely, ZM4 and ZM5, to reveal their analgesic activity and toxicity. Following oral administration, both compounds were effective in reducing significantly (P < 0.05-0.001) acetic acid-induced writhing behavior, hot plate latency test, and formalin-induced paw licking time as antinociceptive indicators in mice and rats, respectively. Regarding the toxicity, the acute (20, 50, and 150 mg/kg) and repeated oral administration (10, 20, and 50 mg/kg) of these compounds for ten days did not produce any mortality and the compounds were considered well tolerated. However, repeated oral administration of 50 mg/kg of both compounds induced erythropoiesis by means of increasing significantly red blood cells, hemoglobin, and packed cell volume. Moreover, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic and anti-inflammatory activity compared to indomethacin as a positive control. The results indicate that ZM4 and ZM5 possess potential analgesic activity while being preliminarily safe and have minimal ulcerogenic activity.

No MeSH data available.


Related in: MedlinePlus

Percent of increase in latency periods of mice treated with normal saline (negative control), aspirin (positive control), ZM4, and ZM5. Treated mice were challenged on a hot plate every 15 min for 1 hour after oral treatment. Values are expressed as mean ± S.E.M (n = 9). *P < 0.05, and **P < 0.01 against normal saline and  +P < 0.05 ZM4 and ZM5 against aspirin.
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fig3: Percent of increase in latency periods of mice treated with normal saline (negative control), aspirin (positive control), ZM4, and ZM5. Treated mice were challenged on a hot plate every 15 min for 1 hour after oral treatment. Values are expressed as mean ± S.E.M (n = 9). *P < 0.05, and **P < 0.01 against normal saline and  +P < 0.05 ZM4 and ZM5 against aspirin.

Mentions: The results of the hot plate test show that oral administration of aspirin (200 mg/kg), ZM4, and ZM5 (both at 20 mg/kg) produced a significant (P < 0.05) increase in latency times especially at 45–60 min after administration (Figure 3). It was noticed that ZM4 showed a fast onset of action and increased significantly the % of latency period after 15 min of administration. The effect of ZM4 continued to increase in a linear-like pattern during the testing period where it increased the latency period by 82% compared to the recorded initial latency periods at the end of 60 min testing time (P < 0.01). Both ZM4 and ZM5 showed more pronounced effects than aspirin (200 mg/kg). However, a statistically significant difference between the tested compounds and the positive control was detected only after 60 min of the oral administrations (Figure 3).


Analgesic and Toxicity Studies of Aminoacetylenic Isoindoline-1,3-dione Derivatives.

Shakir R, Muhi-Eldeen ZA, Matalka KZ, Qinna NA - ISRN Pharmacol (2012)

Percent of increase in latency periods of mice treated with normal saline (negative control), aspirin (positive control), ZM4, and ZM5. Treated mice were challenged on a hot plate every 15 min for 1 hour after oral treatment. Values are expressed as mean ± S.E.M (n = 9). *P < 0.05, and **P < 0.01 against normal saline and  +P < 0.05 ZM4 and ZM5 against aspirin.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539427&req=5

fig3: Percent of increase in latency periods of mice treated with normal saline (negative control), aspirin (positive control), ZM4, and ZM5. Treated mice were challenged on a hot plate every 15 min for 1 hour after oral treatment. Values are expressed as mean ± S.E.M (n = 9). *P < 0.05, and **P < 0.01 against normal saline and  +P < 0.05 ZM4 and ZM5 against aspirin.
Mentions: The results of the hot plate test show that oral administration of aspirin (200 mg/kg), ZM4, and ZM5 (both at 20 mg/kg) produced a significant (P < 0.05) increase in latency times especially at 45–60 min after administration (Figure 3). It was noticed that ZM4 showed a fast onset of action and increased significantly the % of latency period after 15 min of administration. The effect of ZM4 continued to increase in a linear-like pattern during the testing period where it increased the latency period by 82% compared to the recorded initial latency periods at the end of 60 min testing time (P < 0.01). Both ZM4 and ZM5 showed more pronounced effects than aspirin (200 mg/kg). However, a statistically significant difference between the tested compounds and the positive control was detected only after 60 min of the oral administrations (Figure 3).

Bottom Line: We have developed a series of aminoacetylenic isoindoline-1,3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines.Moreover, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic and anti-inflammatory activity compared to indomethacin as a positive control.The results indicate that ZM4 and ZM5 possess potential analgesic activity while being preliminarily safe and have minimal ulcerogenic activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, Petra University, P.O. Box 961343, Amman 11196, Jordan.

ABSTRACT
We have developed a series of aminoacetylenic isoindoline-1,3-dione compounds and showed their anti-inflammatory activities by reducing carrageenan-induced rat paw edema and modulating proinflammatory and anti-inflammatory cytokines. In the present study and due to efficacy reasons, we are exploring only two of these compounds, namely, ZM4 and ZM5, to reveal their analgesic activity and toxicity. Following oral administration, both compounds were effective in reducing significantly (P < 0.05-0.001) acetic acid-induced writhing behavior, hot plate latency test, and formalin-induced paw licking time as antinociceptive indicators in mice and rats, respectively. Regarding the toxicity, the acute (20, 50, and 150 mg/kg) and repeated oral administration (10, 20, and 50 mg/kg) of these compounds for ten days did not produce any mortality and the compounds were considered well tolerated. However, repeated oral administration of 50 mg/kg of both compounds induced erythropoiesis by means of increasing significantly red blood cells, hemoglobin, and packed cell volume. Moreover, these compounds did not induce gastric lesions in the stomach of experimental animals at the doses that exhibited analgesic and anti-inflammatory activity compared to indomethacin as a positive control. The results indicate that ZM4 and ZM5 possess potential analgesic activity while being preliminarily safe and have minimal ulcerogenic activity.

No MeSH data available.


Related in: MedlinePlus