Pharmacological rational of dry ripe fruit of Aegle marmelos L. as an anti-nociceptive agent in different painful conditions.

The aim of study is to investigate central and peripheral analgesic effects of methanolic extract of dry ripe fruit of Aegle marmelos Linn. Corea (Am. Cr) by two methods, tail flick test and acetic acid induced writhing test at 100, 250 and 500mg/kg doses in animal models. Analgesic activity against tail flick test revealed that Am. Cr induced significant increase in latency period in dose dependent manner i.e. 65.38% at 100mg/kg, 395.37% at 250mg/kg (p<0.01) and 459.25% at 500mg/kg (p<0.01) body weight at 1hr after drug delivery while at 2hr effect decreased i.e. 61.53% at 100mg/kg, 161.11% (p<0.01) at 250mg/kg and 165.74% (p<0.01) at 500mg/kg but interestingly again there is an elongation in latency period at 3hr i.e. 106.15% at 100mg/kg dose, 251.85% (p<0.01) at 250mg/kg and 293.51% (p<0.05) at 500mg/kg respectively. The standard drug Diclofenac sodium at the dose of 5mg/kg continuously increased the latency period but less significantly as compared to the test substance i.e. 79.43%, 113.08% and 222.42% (p<0.05) respectively. Acetic acid induced writhing test produced highest significant activity at the dose of 100mg/kg i.e. 89.83% (p<0.01) as compared to Diclofenic sodium (standard drug) at a dose of 5mg/kg body weight i.e 63.63% (p<0.01). It is concluded that dry ripe fruit of A. marmelos possesses significant dual analgesic activities i.e. central and peripheral.

Synthesis and smooth muscle-selective relaxant activity of a piperidine analogue: 1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride.

The antispasmodic and vasodilator activities of a newly synthesized piperidine derivative (1-(4'-fluorophenacyl)-4-hydroxy-4-phenyl-piperidinium chloride) were studied in vitro. The test compound exhibited a dose-dependent relaxant effect on the spontaneous and K+ (75 mM)-induced contractions of isolated rabbit jejunum with respective EC50 values of 0.01 mM (0.01-0.02, 95% Cl) and 0.30 mM (0.17-0.56). The Ca++ channel blocking (CCB) activity was confirmed when the test compound (0.1-0.2 mM) shifted the Ca++ dose-response curves to the right, similar to that produced by verapamil (0.1-1.0 microM), a standard CCB. In the isolated rabbit aorta, the test compound showed a dose-dependent vasodilator effect on K+ (75 mM)-induced contractions with an EC50 value of 0.08 mM (0.02-0.26) while also suppressed the norepinephrine (1 microM) control peak responses with EC50 value of 0.08 mM (0.05-0.13, n=5). When tested in Langendorff perfused rabbit heart preparation, the test compound exhibited a negligible inhibitory effect on the rate or force of atrial and ventricular contractions when tested up to 5 mM. The results show smooth muscle-selective relaxant effect of the test compound on intestinal and vascular preparations mediated possibly via blockade of voltage and receptor-operated Ca++ channels.