Volume 17 Number 4
SHORT COMMUNICATION The mean anaesthetic I administration prolonged the time was reduced after ha EFFECT OF SOME PSYCHOACTIVE AGENTS ON PENTOBARBITONE promethazine, imipramine a~ ANAESTHESIA IN RATS presented in Table 1.
TABLEI: Influence of RAJE DRA K. RAINA
Drugs (mg/kg., i.p.) Department of Pharmacology, Government Medical College, Srinagar
Summary: Several psycho-active agents we-re investigated fo'r their influence on pentobarbitone Control (Saline 2 ml/kg) anaesthesia time in rats. It was found that prior administration of haloperido.l, methaqualone Methylcellulose (2%) in ormal s and triflupromazine reduced the duration of anaesthesia. An increase in durati~n was noted Promethazine (l0.0 mg) after diazepam. The probable mechanism has been discussed. . Chlorpromazine (5.0 IIIg) Triflupromazine (10.0 mg) Key words: pentobarbitone anaesthesia psychoactive agents Thioproperazine (10.0 mg) Haloperidol (10.0 IIIg) INTRODUCTION Methaqualone (15.0 mg) Diazepam (10.0 mg.) Kato and Chiesara (7) reported that many centrally active agents may produce tolerance to Imipramine (10.0 mg) barbiturates as a result of induction of liver microsomal enzymes involved in drug metabolism Haloperidol and promethazine have also been reported to influence the enzyme activity (6).
As there is lack of information concerning the effect of various psycho-active agents on metabolic The results obtained mechanisms, it was thought of interest to study the influence of some of the commonly used after pretreatment with agents on pantobarbitone anaesthetic time and if possible to attempt to correlate the data servations made by Kato ar obtained with the results on enzyme activity reported in the literature. result since prior administ MATERIALS AND METHODS in the duration of anaestht pentobarbitone anaesthe ia This study was conducted on 69 albino rats (100-200 g) of either sex. Groups of barbitone sleeping time (I animals received an intraperitoneal injection of a psychoactive agent for three consecutive vation is in conformity wi days. On the fourth day, all the animals were given pentobarbitone odium (Abbot) 20 mg/kg only in ea e of diazepam. (ip) and the interval between loss of righting reflex and its subsequent recovery was noted by tion (1) caused a reductic the method of Dandiya and Cullumbine (4). after haloperidol. The ability of drul Diazepam (Sigma) 10 mgjkg, methaqualone (Boots) IS mg/kg, promethazine HCI is paralleled in 1'i1'O by cl (M&B) 10 mgjkg, chlorpromazine HCI (M&B) S mgjkg, thioproprazine mesylate (M&B) 10 action (2,3,8). Several W mgjkg; triflupromazine HCI (Squibb) 10 mg/kg, imipramine HCI (Geigy) 10 mgjkg and haloperidol metabolism of pentobarb (Searle) 10 mgjkg (in suspen ion with 2 per cent methylcellulose in normal saline) were used. It has been argued that tl The control group of the animals were pretreated with saline (2 mllkg ip). The experiments were carried at a room temperature of IS-20'C. induced by drugs whio changes noted in the dur enzyme inductionjrepressi
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RESULTS
The mean anaesthetic time in the control group was 53.7 ± 5.70 mm. Prior diazepam administration prolonged the duration of anaesthesia significantly (P TABLE I: InR uence of some psychoactive agents on pentobarbitone anaesthesia in rats. ol/ege, Srinagar Drugs (mgjkg., i.p.) Number of Mean anaesthesia 't' 'p' animals lime±S£Cin min) ence on pentobarbitone Control (Saline 2 ml/kg) 8 • 53.7 et 5.70 loperidol, methaqualone Methylcellulose (2%) in Normal saline(2 ml/kg) 5 47.4± 6.32 0.74 >0.10 in duration was noted Promethazine (10.0 mg) 8 40.3 ±6.01 1.63 >0.10 Chlorpromazine (5.0 I11g) 6 56.2± 12.70 0.17 >0.10 Trifluprornazine (10.0 mg) 7 28.2±4.81 3.50 <0.01 Thioproperazine (10.0 mg) 9 45.7 ± 9.45 0.76 >0.10 Haloperidol (10.0 mg) 7 15.5±2.82 6.11 <0.001 Methaqualone (15.0 mg) 7 27.7± 5.40 3.40 <0.01 Diazepam (10.0 mg.) 7 80.9±7.21 3.06 <0.01 s may produce tolerance to Imipramine (10.0 II1g) 5 41.0± 6.81 1.79 =0.10 olved in drug metabolism ------the enzyme activity (6). DISCUSSION -active agents on metabolic e of the commonly used The results obtained reveal that there was change in pentobarbitone anaesthetic time mpt to correlate the data after pretreatment with diazepam, methaqualone, triflupromazine and haloperidol. The ob- servations made by Kato and Chiesara (7) with chlorpromazine are at variance with the present result since prior administration of chlorpromazine failed to produce any significant change in the duration of anaesthesia. Thioproperazine and imipramine did not significantly influence pentobarbitone anaesthesia. Promethazine which has been earlier reported to reduce pento- either sex. Groups of barbitone sleeping time (6) was observed to be devoid of any action. The foregoing obser- nt for three consecutive vation is in conformity with that of Kato and Chiesara (7). A significant increase was noted sodium (Abbot) 20 mg/kg only in case of diazepam. Methaqualone which has been reported to increase barbiturate oxida- nt recovery was noted by tion (1) caused a reduction in pentobarbitone anaesthetic time. A similar result was noted after haloperidol. kg, promethazine HCI The ability of drugs to stimulate or repress the microsomal metabolizing enzymes zine mesylate (M &B) 10 is paralleled in 1'ivo by changes in the rates of metabolism and variations in duration of drug ) 10mgjkg and haloperidol action (2,3,8). Several workers (5, 3, 7, 8) have tried to correlate the changes induced in the ormal saline) were used. metabolism of pentobarbitone by pretreatment with other agents, with the duration of sicep. "g ip). The experiments It has been argued that the metabolic enzyme systems which inactivate hypnotic barbiturates are induced by drugs which are known to induce microsomal enzymes (2). The foregoing changes noted in the duration of pentobarbitone anaesthesia may be explained on the basis of enzyme induction/repression (2) or change in the activity of metabolic enzymes (la) or inter- ~------) 386 Raina October 1973 SHORT COMMUNICAT/f)N Ind. J. F'hysiol. Pharmac. ference by the psycho active agent with the feed-back regulatory role of the breakdown products of enzymes (9). ACKNOWLEDGEMENTS EFFECf OF 3 I am thankful to the Principal, Government Medical College, Srinagar for permitting me to conduct this study. The author wishes to thank M&B (India), for the generous supply of promethazine, chlorpromazine, thioproprazine, and Sigma (India) and Searle (India) for diazepam and haloperidol respectively. The technical assistance of Sh. N.A. Shah is gratefully acknowledged. Summary: The effect of 30-1 REFERENCES studied in rats. The results 1. Ballinger, B., O.K. Maley, I.H. Stevenson and M.J. Turnball, Stimulation of drug metabolism by ological investigations carrie centrally active drugs. Br. J. Pharmac., 41 : 383, J 971. • significant observation whicl 2. Bums, J.J. and A.H. Conney, Enzyme stimulation and inhibition in metabolism of drugs. Proc. Roy. had low total lipid levelsin Soc. Med., 59 : 955, 1965. . comparison to non·piperazu 3. Conney, A.H. Pharmacological implications of enzyme induction. Pharmac. Rev., ]9 : 317, 1967. 4. Dandiya, P.c. and H. Cullumbine. Studies on Acorus calamus-some pharmacological actions of volatile Key words: piperazine oil. J. Pharmac. Exp. Ther., 125 : 353, 1959. 5. Fouts, J.R. and B.B. Brodie. On mechanism of drug potentiation by iproniazid. J. Pharmac. Exp, Ther., 116 : 480, 1956. 6. Green, W.F. and J.D. Ireson. Pentobarbitone sleeping time after haloperidol and promethazine. Arch. Int. Pharmacodyn Ther., 196 : 112, 1972. Piperazine is widely us 7. Kato, R. and F. Chiesara. Increase of pentobarbitone metabolism induced in rats pretreated with some worm infestation in man anr centrally acting compounds. Br. J. Phannac., 18 : 27. 1962. 8. Prescott, L.F. Pharmacokinetics of drug interaction. Lancet. 2: 1239, 1969. were in use until about the 9. Shuster, L. and H. Jick. Turnover of microsomal reduced nicotinamide adenine dinucleotide phosphate important reasons for its wid cytochrome-c-reductase in liver of mice treated with pentibarbital. J. Bioi. Chem., 241 : 5366, 1966. toward effects have been obs 10. Sladek, N.B. and G. Mannering. J. Ubi. Pharmac., 5: 174, 1969. cited by Green, W.F. and J.D. Ireson. Pentobarbitone sleeping-time after haloperidol and promethazine. Arch. lnt, Pharmacodyn. Ther., 196; made to study the biochem 112, 1972. - This becomes all the more si, requires administration of tl infestation. Some. preliminary biocl Twelve Sprague-Daw the study. They were fed h ghout the 30-day experimen were observed as controls f were given a solution of pip aratna Pharmaceuticals, Er g,h'e a concentration of 3( content in the different tis Laboratory Methods and ------