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RESEARCH LETTER
Year : 2004  |  Volume : 36  |  Issue : 4  |  Page : 246-247
 

Piracetam attenuates minoxidil-induced antinociception in mice


Departments of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India

Correspondence Address:
Departments of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India



How to cite this article:
Rehni AK, Rehni D. Piracetam attenuates minoxidil-induced antinociception in mice. Indian J Pharmacol 2004;36:246-7


How to cite this URL:
Rehni AK, Rehni D. Piracetam attenuates minoxidil-induced antinociception in mice. Indian J Pharmacol [serial online] 2004 [cited 2021 Sep 16];36:246-7. Available from: https://www.ijp-online.com/text.asp?2004/36/4/246/11153


Sir,
Piracetam is a nootropic agent and has been used to treat various dementias for several years as it enhances or facilitates various learning and other cognitive functions.[1] Piracetam has been shown to attenuate the opioid antinociception.[2] Besides, piracetam increases the intracellular ATP concentration in the nerve cell[3] which may have an inhibitory effect over the ATP-gated potassium channels (KATP channels). Therefore, the present study has been designed to investigate the effect of piracetam on the KATP channel opener-induced antinociception. Minoxidil is a selective KATP channel opener[4] and produces antinociception in mice when administered centrally.[5]
Six to eight-weeks-old healthy inbred BALB/c mice ( 253 g) of either sex were used in the study. They were housed in an animal house provided with a 12 h light/dark cycle and had free access to food and water. Minoxidil (Dr. Reddy's Laboratories Ltd., Hyderabad, India) and piracetam (Micro Labs Ltd., Pondicherry, India) were dissolved in normal saline immediately before use. The institutional ethical committee approved all experimental procedures.
Minoxidil was injected i.c.v. in conscious mice in a volume of 10 l with Hamilton syringe as described by Haley and McCormick.[6] Time course studies were used to ascertain peak antinociception as tested by the tail flick test. Peak time for minoxidil was 10 min after injection.
Nociceptive threshold was measured by the tail flick test in mice.[7] The tail flick latency was considered as the time between tail exposure to radiant heat and tail withdrawal. An electrically heated nichrome wire was used as a source of radiant heat in the analgesiometer. The intensity of radiant heat was regulated in order to obtain pretreatment latency between 2 to 3 s. A cut-off latency time was fixed at 10 s. Tail flick latency was expressed as a percentage of the maximum possible effect (MPE):
(Post-treatment latency-
Pretreatment latency)
MPE (%) =-------------------------------------- x 100
(Cut off time- Pretreatment latency)
Mice were divided into 6 groups of 5 each. Group I was administered 10 l of vehicle i.c.v. and served as vehicle control. Group II was administered minoxidil, 25 g/mouse, i.c.v. and served as a control for piracetam-treated groups. Groups III, IV, V and VI were administered minoxidil, 25 g/mouse, i.c.v. 30 min after the administration of 125, 250, 500 and 1000 mg/kg, i.p. of piracetam respectively. Tail flick latency was observed before and 10 min after minoxidil administration. One-way ANOVA and Student's 't' test were used to determine the significance of the difference between the values of the various groups. P values <0.05 were considered significant.
Minoxidil (25 g/mouse, i.c.v.) produced significant increase in % MPE as compared to vehicle-treated controls. Piracetam significantly attenuated minoxidil-induced antinociception. The attenuation was found to be dependent on the dose of piracetam [Table - 1].

The results of the present study demonstrate that minoxidil-induced antinociception was dose-dependently attenuated by piracetam. It has been demonstrated that minoxidil-induced antinociception is attenuated by KATP channel blocker, glyburide and opioid antagonists, thus indicating the possible role of KATP channels and released endogenous opioids.[8] KATP channel openers have also been shown to potentiate opioid analgesia whereas naloxone and antisense to block the KATP channel opener-induced antinociception.[9],[10] Piracetam has also been shown to attenuate opioid analgesia.[2] Moreover, at higher concentrations piracetam has showed to have an affinity to bind to opioid receptors.[11] Besides, piracetam also increases the intracellular ATP concentration in the nerve cell[3] which may have an inhibitory effect over the KATP channels. Thus, it may be suggested that piracetam attenuates minoxidil-induced antinociception by a mechanism related to the antagonism of endogenous opioids, possibly through a KATP channel-linked mechanism. Further study is however required to elucidate this effect of piracetam.


  Acknowledgements Top


The authors are grateful to Dr. N. K. Talwar, Punjab Veterinary Vaccine Institute, Punjab Agriculture University, Ludhiana for technical help and animal house and laboratory facilities. 

  References Top

1.Noble S, Benfield P. Piracetam. CNS Drugs 1998;9: 497-511.  Back to cited text no. 1    
2.Chichenkov ON, Krylova IN, Borozdin MIu, Pokatilov DV. The influence of piracetam on the effects of narcotic analgesics. Farmakol Toksikol 1990;53:22-4.  Back to cited text no. 2  [PUBMED]  
3.Gabryel B, Adamek M, Pudelko A, Malecki A, Trzeciak HI. Piracetam and vinpocetine exert cytoprotective activity and prevent apoptosis of astrocytes in vitro in hypoxia and reoxygenation. Neurotoxicology 2002;23:19-31.  Back to cited text no. 3  [PUBMED]  
4.Newgreen DT, Bray KM, McHarg AD, Weston AH, Duty S, Brown BS, et al. The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim. Br J Pharmacol 1990; 100:605-13.  Back to cited text no. 4  [PUBMED]  
5.Campbell VC, Welch SP. The role of minoxidil on endogenous opioid peptides in the spinal cord: a putative co-agonist relationship between K-ATP openers and opioids. Eur J Pharmalcol 2001;417:91-8.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Haley TJ, McCormic WG. Pharmacological effect produced by intracerebral injection of drugs in conscious mouse. Br J Pharmacol 1957; 12:12-5.  Back to cited text no. 6    
7.D'Amour FE, Smith DL. A method for determining loss of pain sensation. J Phamacol Exp Ther 1941;72:74-7.  Back to cited text no. 7    
8.Welch SP, Dunlow LD. Antnociceptive activity of intrathecally administrered potassium channel openers and opiod agonists: a common mechanism of action? J Pharmacol Exp Ther 1993; 267:390-9.  Back to cited text no. 8  [PUBMED]  
9.Lohmann AB, Welch SP. Antisenses to opioid receptors attenuate ATP-gated K(+) channel opener-induced antinociception. Eur J Pharmacol 1999;384:147-52.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Lohmann AB, Welch SP.ATP-gated K(+) channel openers enhance opioid antinociception: indirect evidence for the release of endogenous opioid peptides. Eur J Pharmacol 1999; 385: 119-27.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Bering B, Muller WE. Interaction of piracetam with several neurotransmitter receptors in the central nervous system. Relative specificity for 3H-glutamatesites. Arzneimittelforschung 1985; 35:1350-2.  Back to cited text no. 11  [PUBMED]  
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