Pharmacodynamic Effects of Piperazine Citrate on the

Journal of HEALTH AND VISUAL SCIENCES ______________________ JOURNAL OF HEALTH AND VISUAL SCIENCES (2008) VOL 10 (3): 1-6

Pharmacodynamic Effects of Piperazine Citrate on the Vascular Smooth Muscle of the Rat S. Ghasi*, C.P. Chijioke and C.A. Anusiem Department of Pharmacology and Therapeutics, College of Medicine, University of Nigeria, Enugu, Nigeria.

Abstract Effects of piperazine citrate on the vascular smooth muscle using rat hindquarters was investigated. Piperazine caused dose-dependent increases in flow rate of 51.69  2.59, 89.33  6.23 and 200.4  13.12 % respectively for doses 2, 5 and 10g over the control values indicating vasodilatation. Compared to the value from control animals (2.36  0.57%) these values were statistically significant using Student’s ‘t’ test (P < 0.0001). At peak activity, adrenaline 2g caused an average fall in flow rate of 49.0  3.02% indicating vasoconstriction. Various doses of piperazine citrate antagonized this effect. The average % increases in flow rate due to the intervention with piperazine 2g and 5g were 32.02  2.99 and 61.1  3.63 respectively. The average flow rates (ml/5min) caused by adrenaline 2g before piperazine 2 and 5g were added were 2.2  0.46 and 2.48  0.21 respectively. Piperazine 5g induced a statistically significant increase in flow rate 10 minutes later to 4.0  0.36 ml/5min (P=0.0064). The average increase produced by piperazine 2g was, however, not statistically significant (P=0.3673). Keywords: Piperazine citrate, Vascular smooth muscle, Rat hindquarters Received 15 July 2008; accepted after revision 12 November 2008

Introduction Piperazine is a cheap anthelmintic agent active against Ascaris lumbricoides and Enterobius vermicularis. It has been shown to have nonspecific non-vascular smooth muscle relaxant activity brought about by its ability to directly cause the depression of non-vascular smooth muscle 1. _________ *Corresponding Author

The electrocardiographic patterns of piperazine citrate in both human volunteers and laboratory animals, and the antiarrhythmic potentials of the drug in anaesthetized rats showed that piperazine citrate has antiarrhythmic activity brought about by prolongation of repolarization2-4. It decreased the heart rate of the rat but significantly prolonged the duration of the P-R, Q-Tc, and J-T intervals. It, however, had no effect on the QRS complex. Drugs

Ghasi et al/ Journal of Health and Visual Sciences, (2008) Vol. 10 (3): 1-6 that prolong repolarization usually do so by blocking the potassium channels, and this may explain the non-specificity of the piperazine action. On the pressure of the anaesthetized cat, piperazine citrate showed a dose-dependent decrease on the arterial blood pressure5. The hypotensive effect was always transient returning to the equilibration level within two minutes. The reduction of the blood pressure could, therefore, be due to relaxation of vascular smooth muscle or depression of the myocardium. In the present study we examined the effect of piperazine citrate on the vascular smooth muscle of the rat.

Materials and Methods Rats of either sex weighing between 180 and 250g were killed by a blow on the head. The throats were cut and the blood allowed to drain out. The abdominal cavity was opened via a longitudinal incision extending from the sternum to the anus. The inferior and superior mesenteric arteries were divided between ligatures. The abdominal viscera were then removed exposing the abdominal aorta, which was cannulated. The body wall and vertebral column were transected above the point of cannulation and the cannula filled with heparinized saline (10 i.u. /ml) and connected to the perfusion system by means of fine rubber tubing. The hindquarters preparations were placed on wire mesh on a glass funnel to enable collection of the fluid with a measuring cylinder. This is a modification necessitated by the fact that our electronic Thorpe drop recording assembly was faulty. The hindquarters preparation was then connected to a perfusing apparatus. The perfusing fluid was oxygenated Ringer-Locke solution (NaCl 9.0, KCl 0.42, CaCl2 0.24, NaHCO3 0.5, Glucose 1g /litre). Care was taken to exclude air bubbles before the arterial cannula of the perfusion apparatus was connected to the rat hindquarters preparation. The pressure at which physiological fluid passed through the vessels was kept constant in all the experiments. Drug-induced alterations in the rate of outflow of the perfusing fluid were recorded every 5 min. The rate of flow of fluid to the injection cannula was controlled by a tap, which was adjusted at the beginning of each experiment to a suitable rate. A uniform outflow was obtained for at least 15 min before any of the test drugs was injected.

The drugs were administered as bolus doses in volumes not exceeding 0.2ml. In the first set of experiments designed to serve as control, saline 0.2ml was injected and the effect was observed for 30 min. Next, the effects of piperazine 2, 5, and 10µg were studied. The effects of piperazine 2 and 5µg and phentolamine 20 and 100g following treatment with adrenaline were also studied.

Result During the 30min. period of observation piperazine caused dose-dependent increases in flow rate, measured as average % change in flow rate over the value at equilibration. The mean  SEM of average % increases for piperazine 2, 5 and 10g bolus injection were 51.69  2.59, 89.33  6.23 and 200.4  13.12 % respectively. Compared to the value from control animals (2.36  0.57%) they were statistically significant using Student’s ‘t’ test (P < 0.0001). One-way analysis of variance (ANOVA) showed that the vasodilatation caused by various doses of piperazine was concentrationdependent (P < 0.0001). Further analysis to determine extent of variance using Bonferroni’s multiple comparison test showed that piperazine 2g, compared with piperazine 5g, had a P value less than 0.05, while piperazine 2g and 5g versus the 10g dose in each case was even more significant (P < 0.001). The average % peak changes of the various preparations administered with piperazine 2g, 5g and 10g over values at equilibration were also evaluated and found to be 60.34  2.45, 106.1 2.77 and 246.2  12.81 respectively. The difference between each of these values and the control value of 3.78  0.53 for the preparations that received normal saline was statistically significant (P