ABSTRACT
PURPOSE: Glaucoma is characterized by increased intraocular pressure (IOP). The effect of nicorandil and pinacidil on IOP in experimentally induced acute and chronic models of glaucoma and the mechanism of action involved were studied. METHODS: New Zealand white rabbits were used for the study. After the measurement of IOP, nicorandil (1%), pinacidil (1%), and pilocarpine as standard (1%) were instilled topically into the left eye. The other eye served as control. Dextrose (5%) was used to induce acute glaucoma. IOP changes were recorded every 15 minutes until the pressure became normal. Freshly prepared α-chymotrypsin solution was introduced in the posterior chamber to induce chronic glaucoma. Rabbits with ocular hypertension were selected for the study. Similar drug solutions were used to study the effect on IOP. Glibenclamide, pilocarpine, and indomethacin (1%) were used to study the mechanism of action of both drugs. The IOPs were measured just prior to drug instillation and at suitable time intervals using a tonometer. RESULTS: Pretreatment with topical nicorandil and pinacidil significantly lowered the rise in IOP in the acute model. Nicorandil and pinacidil initially caused rise in IOP for 15-30 minutes in chronic glaucoma. This was followed by reduction in IOP. Pretreatment with indomethacin and pilocarpine did not modify the effect of nicorandil and pinacidil on IOP. Pretreatment with glibenclamide blocked IOP from the lowering effect of nicorandil and pinacidil. CONCLUSION: The oculohypotensive effect shown by these drugs appears to be attributable to enhancement of the aqueous humor outflow. This effect is perhaps mediated through potassium channels.
ABSTRACT
Roots of Premna integrifolia Linn. Mant. (Verbanacea) are important rasayana (Adaptogenic) drugs and are considered to be useful in the treatment of variety of ailments. The present study was aimed at evaluating the for its anti-inflammatory and antioxidant activities. Pretreatment with a single dose of methanolic extract of P. integrifolia (PIM) (300 mg/kg b.w.) produced significant inhibition on carrageenan-induced rat hind paw edema, histamine induced wheal formation, and acetic acid-induced mouse vascular permeation. In a 7-day study, daily administration of PIM suppressed formalin induced paw edema and cotton pellet-induced rat granuloma formation. The extract also showed significant inhibition of cyclo-oxygenase (COX-I) activity on rat uterus and plasma membrane stabilization. Apart from this, the antioxidant activity (in vitro) of the extracts was evaluated using the anti radical, superoxide scavenging, erythrocyte membrane stability, anti lipid peroxidation, hydroxyl radical scavenging, nitric oxide scavenging and reducing power (ferric thiocynate method and ß-carotene bleaching test) assays. PIM showed significant anti-oxidant activity. In addition, PIM (300mg/kg b.w.) produced no observable sub acute toxicity in mice with in 15 days. The results scientifically demonstrated the antiinflammatory activity of P. integrifolia roots in various experimental models probably through their antihistaminic, antikinin, COX-inhibitory and antioxidant action. This therefore justifies the folkloric use of the plant.
