Antinociceptive Effect of Promethazine in Mice

Document Type : Original Article


1 School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

2 Young Researchers Club, Islamic Azad University, Kermanshah branch, Iran

3 School of Medicine, Hamedan University of Medical Sciences, Hamedan, Iran


The present study was undertaken to investigate the nociception activity of promethazine, a tranquillizer devoid of hypnotic activity in mice.
Materials and Methods
Antinociception was evaluated, using the acetic acid-induced writhing, tail flick, hot plate and formalin pain tests.
Promethazine (4 and 6 mg/kg) and acetylsalicylic acid (100 mg/kg) produced a significant inhibition of the second phase response in the formalin pain model (P<0.05) and the drug couldn’t show an antinociceptive effect in the first phase. Morphine (10 mg/kg) inhibited both first and second phase response (P<0.01). Drug also showed a dose-dependent inhibition of acetic acid-induced abdominal writhes. The tail flick and hot plate latency weren’t different from control (P>0.05) and administration of naloxone (0.1 mg/kg) couldn't block the antinociceptive effect of promethazine.
The data obtained suggest that antinociceptive effects of the promethazine may be mediated via peripheral and not central mechanisms.


1.Domaj MI, Glassco W, Aceto MD, Martin BR. Antinociceptive and pharmacological effects of metanicotina, a selective nicotine agonist. J Pharmacol Exp Ther 1999; 291:390-398.
2.Dahl V, Reader JC. Non-opioid postoperative analgesia. Acta Anaesthesiol Scand 2000; 44:1191- 1203.
3.Suojaranta-Ylinen R, Hendolin H, Tuomisto L.The effects of morphine, morphine plus scopolamine, midazolam and promethazine on cerebrospinal fluid histamine concentration and postoperative analgesic consumption. Agents Actions 1991; 33:212-214.
4.Santiago-Palma J, Fischberg D, Kornick C, Khjainova N, Gonzales G. Diphenhydramine as an analgesic adjuvant in refractory cancer pain. J Pain Symptom Manage 2001; 22:699-703.
5.Chambers HF. Drugs with important actions on smooth muscle. In: Katzung BG. editor. Basic and clinical pharmacology. New York: McGraw-Hill; NY; 2007.p.386-389.
6.Sansone M, Castellano C, D'Amato FR. Enhancement of morphine-induced hyperactivity by antihistaminic drugs in mice. Arch Int Pharmacodyn Ther 1986; 284:239-245.
7.Malec D. The influence of histamine receptor antagonists on antinociceptive action of narcotic analgesics. Pol J Pharmacol Pharm 1987; 39:229-235.
8.Leza JC, Lizasoain I, Lorenzo P. H1- and H2-histamine receptor blockers and opiate analgesia in mice. Methods Find Exp Clin Pharmacol 1990;12:671-678. 
9.Yeh S. The effect of antihistaminic drugs on pentazocine anticociception in the rat. Pharmacol Biochem Behave 1986; 24:925-927.
10.Koster R, Anderson M, DeBeer EJ. Acetic acid analgesic screening. Fed Proc 1959; 18:418- 420.
11.Shibata M, Ohkubo T, Takahashi H, Inoki R. Modified formalin test; characteristic biphasic pain response. Pain 1989; 38:347-352.
12.Vianna GSB, doVale TG, Rao VSN, Matos FJA. Analgesic and antiinflammatory effects of two chemotypes of Lippia alba: a comparative study. Pharm Biol 1998; 36:347-351.
13.Xiaohong C, Geller BE, MW Adler. Nociceptin/orphanin FQ blocks the antinociception induced by mu, kappa and delta opioid agonists on the cold water tail-flick test. Eur J Pharmacol 2007; 557:32-36.
14.Eddy NB, Leimbach D. Synthetic analgesics II. Dithienylbutenyl and dithi-enylbutylamines. J Pharmacol Exp Ther 1953; 107:385-393.
15.Dharmasiri MG, Jayakody JRAC, Galhena G, Liyanage SSP, Ratnasooriya WD. Anti-inflammatory and analgesic activities of mature fresh leaves of Vitex negundo. J Ethnopharmacol 2003; 87:199-206.
16.Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K. The formalin test: an evaluation of the method. Pain 1992; 51:5-17.
17.Santos ARS, Filho VC, Niero R, Viana AM, Morenof N, Campos MM, Yunes RA, Calixto JB. Analgesic effects of callus culture extracts from selected species of Phyllanthus in mice. J Pharm Pharmacol 1994; 46:755-759.
18.Chang JY, Lewis AJ. Pharmacological methods in the control of iinflammation (modern methods in pharmacology). New York: Wiley-Liss; 1989.
19.Paalzow GH, Paalzow LK. Promethazine both facilitates and inhibits nociception in rats: effect of the testing procedure. Psychopharmacology (Berl) 1985; 85:31-36.