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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

Photographs of open rat stomachs following 3-day administration of (a) normal saline, (b) indomethacin, (c) ZM4, and (d) ZM5. Arrows in photograph (b) indicate examples of full mucosal ulcers induced by indomethacin treatment.
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fig5: Photographs of open rat stomachs following 3-day administration of (a) normal saline, (b) indomethacin, (c) ZM4, and (d) ZM5. Arrows in photograph (b) indicate examples of full mucosal ulcers induced by indomethacin treatment.

Mentions: The gastric effects of oral administration of ZM4 into rats were similar to normal saline administered control group (0.2 ± 0.1 UI for both treatments). However, oral administration of ZM5 into rats induced a minimal hyperemia (0.4 ± 0.1 UI) in comparison to severe full mucosal ulcers induced by 20 mg/kg indomethacin (3 ± 0.4 UI) (Figure 5).


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

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

Photographs of open rat stomachs following 3-day administration of (a) normal saline, (b) indomethacin, (c) ZM4, and (d) ZM5. Arrows in photograph (b) indicate examples of full mucosal ulcers induced by indomethacin treatment.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: Photographs of open rat stomachs following 3-day administration of (a) normal saline, (b) indomethacin, (c) ZM4, and (d) ZM5. Arrows in photograph (b) indicate examples of full mucosal ulcers induced by indomethacin treatment.
Mentions: The gastric effects of oral administration of ZM4 into rats were similar to normal saline administered control group (0.2 ± 0.1 UI for both treatments). However, oral administration of ZM5 into rats induced a minimal hyperemia (0.4 ± 0.1 UI) in comparison to severe full mucosal ulcers induced by 20 mg/kg indomethacin (3 ± 0.4 UI) (Figure 5).

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