Indian J Physiol Pharmacol 2001; 44 (3): 381-382

LETTER TO THE EDITOR

EFFECT OF a-MPT ON IMIPRAMINE INDUCEDANTINOCICEPTION IN RATS

Sir,

(Received on November 27,2000)

Neurophysiological and pharmacologicalevidence have demonstrated that themain neurotransmitters implicated indescending pain control are serotonin (5HT),noradrenaline (NA) and the endogenousopioids, although others may also play arole. Involvement of serotonergic andnoradrenergic mechanism have beenimplicated in morphine (1) and nicotine (2)induced antinociception. Imipramine, atricyclic antidepressant, is shown toproduce antinociception in animalexperiments (3). It inhibits 5HT and NAuptake. Our previous study (unpublisheddata) has shown that both ondansetron(5HT3 antagonist) and serotonin biosynthesisinhibitor parachlorophenylalanine (PCPA)pretreatment inhibits the antinociceptiveaction of imipramine. In the present study,we have investigated the effect of a-methyl-para-tyrosine (a-MPT), an inhibitor ofNA synthesis, on imipramine inducedantinociception, to ascertain the role ofnoradrenergic mechanism.

Healthy male albino rats of wistarstrain (200-250 gms) were divided into fivegroups. Animals were kept under standardlaboratory conditions. Group 1 receivednormal saline (1 ml/kg, I.P.). Group 2-4received im ip r arn in e 2 mg, 5 mg and10 mg/kg I.P., respectively. Imipramine 10mg/kg was chosen for subsequentexperiments. Group 5 animals received a-

MPT in a dose of 250 mg/kg twice 12 hoursapart (4). Imipramine 10 mg/kg wasadministrated two hours after the last doseof a-MPT. All the drugs were dissolved innormal saline. The time course effect ofimipramine alone and pretreatment of a-MPTon the latency of tail flick response wasstudied. In the tail flick test (thermalnociception), the rat was placed on tail flickapparatus (Techno), radiant heat was appliedto a portion of the tail (about 5 cm from thetip) (5) and the latency of tail flick response(TFL) was noted for each rat at 0 (pre drug),15, 30, 60, 90 and 120 minutes after drugadministration. The cut off point was 20seconds and six rats were used for each doseresponse. The area under the curve (AUC,see) of the tail flick latency was determined.by using traphezoidal rule. Results areexpressed as mean ± SE and unpaired 't' testwas applied for comparison between groups.P<0.05 was considered statisticallysignificant. In the present study, imipraminecaused a dose related increase in the tailflick latency in rats (Fig. 1). AUC ofimipramine 2 mg/kg was 558 ± 21.3;imipramine 5 mg/kg was 653.8 ± 26.7 andimipramine 10 mg/kg was 732.8 ± 39.6. AUCof control was 551.9 ± 22.63. Prioradministration of a-MPT to rats decreasedthe AUC of imipramine (10 mg/kg)from 732.8±39.6 to 418.05 ± 49.06 (P<0.05)(Fig. 1). a-MPT alone did not modify tailflick latency.

382 Letter to the Editor

900o Control

800 *IZllmipramine 2 mglkg

iiJ 700

tn B Imipramine 5 mg/kg+ 600~U III Imipramine 10 mgJkgQ) 500~ !!Ia -MPT (250 mglkg) +...J

imipramine (10 mglkg)u, 400I-..0 300U::lc( 200

100

0

·p<0.05 as oompared to control·~p<0.05 as compared to imipramine 10 mglkg

Fig. 1: Modification by Il-MPT of anti-nociceptiveresponse of imipramine (AUC, M ± SE) ontail flick latency (TFL) in rats.

Indian J Physiol Pharmacol 2000; 44(3)

Imipramine is a tricyclic antidepressant. It'santidepressant action is believed to be as aresult of blockade of reuptake of 5HT andNA. In animal experiments imipramine isshown to produce antinociception (3). Studieshave shown that the descending inhibitorysystems in the pain pathways are in partnoradrenergic and serotonergic (6-8). Ourprevious study (unpublished data) has shownthe involvement of serotonergic mechanismin imipramine induced antinociception. Thepresent study was conducted to ascertain ifnoradrenergic mechanisms are involved inthe imipramine induced antinociception. Inthe present study, pretreatment with a.-MPTdecreased the antinociceptive effect ofimipramine, suggesting that at least a partof imipramine antinociceptive effect may bemediated through noradrenergic mechanism.

LEKHA SAHA, V. K. BHARGAVA* AND RATNESH KUMARDepartment of Pharmacology,

PGlMER, Chandigarhn - 160 012

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*Corresponding Author