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" Evaluatio of analgesic effect of trifluoperazine as a calmodulin inhibitor "
/سعید گلبیدی
; taghi Ghafghazi, Valiollah Hajhashemi
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Isfahan University of Medical Sciences
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| Document Type
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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102524
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| Doc. No
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T7417
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| Call number
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QV,77.9,G617e,2001
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| Main Entry
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Golbidy, Saeid
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| Title & Author
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Evaluatio of analgesic effect of trifluoperazine as a calmodulin inhibitor/سعید گلبیدی
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| College
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Schools, Pharmacy
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| Date
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, 2001
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| Degree
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Pharmacology, PHD
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| Page No
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VII, 134 P.: tab, diag
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| Abstract
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Introduction: The main aim of the present work to clarify whether the blockade of calmodulin is involved in the analgesic effect of tirfluoperazine or not. In this regard, we compared the analgesic effect of trifluoperazine with those of, a specific D2 dopamine receptor antagonist, an anticholinergic agent, an a- adrenergic receptor antagonist, an antihistaminic, and a specific calmodulin inhibitor, Also, we examined the effects of histamine, physostigmine, bromocriptine, norepinephrine and calcium on trifluoperazine- induced analgesia. Methods: The effects of various agents of formalin and light tail flick test were evaluated one hour after intraperitoneal (i.p) and fifteen minutes after intrathecal (i.t) and intracerebroventricular (i.c.v) drug administration. We also used rotarod to quantify motor side effects of the drugs. Result: The effects of i.t. administration of various agents before formalin test are as follows: trifluoperazine showed analgesia in the relatively low doses and hyperalgesia in the higher dose. All doses of sulpiride induced hyperalgesia. Atropine, phentolamine and brompheniramine failed to produce analgesia. Calmidazolium showed significant analgesia in a dose- dependent manner. Histamine, physositigmine, bromocriptine and norepinephrine did not affect trifluoperazine- induced analgesia. Meanwhile, calcium attenuated the analgesic effects of trifluoperazine and inhibited calmidazolium- induced antinociception. These drugs (after intrathecal administration) had relatively similar effects on light tail flick test. We also examined the effect of above drugs on formalin and light tail flick tests after i.c.v. and i.p. injections. Lower doses of trifluoperazine induced higher degree of analgesia in these tests too, but calmidazolium did not show any significant effect. Discussion: The main aim of this study was to clarify the role of calmodulin inhibition in trifluoperazine induced analgesia. In our experiments, only i.t. calmidazolium showed analgesic effects. Therefore, we have paid much more attention to the mechanisms, which might be involved in spinal component of trifluoperazine- induced analgesia and have discussed possible relation of this effect to the various properties of this drug. In this experiment i.t. trifluoperazine showed biphasic effects i.e. analgesia in relatively low doses and hyperalgesia in the higher dose. Sulpiride, atropine, phentolamine and brompheniramine were devoid of analgesic effect and even induced hyperalgesia in some cases. In addition i.t. bromocriptine, physostigmine, norepinephrine and histamine did not affect trifluoperazine induced analgesia. Therefore, it seems unlikely that the antinociceptive effect of trifluoperazine is mediated through its antidopaminergic, anticholinergic, antiadrenergic, and antihistaminic properties. In our experiment the i.t. administration of calmidazolium induced a dose dependent decrease of the nociceptive responses. In addition, this effect of calmidazolium was inhibited by simultaneous administration of calcium. Trifluoperazine- induced analgesia also was attenuated by calcium. These suggest that calmodulin activation in the spinal cord is involved in the development of pain in both formalin and light tail flick test and supports the possibility that analgesia produced through calmodulin inhibition may partially contribure to the spinal component of trifluoperazine- induced analgesia.
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Trifluoperazine
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| Descriptor
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Analgesics داروهای ضد درد
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Injection, spinal تزریق نخاعی
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Receptors, dopamine گیرندههای دوپامین
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Trifluoperazine
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Calmodulin
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| Added Entry
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Ghafghazi, Taghi
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| Translated Title Supplied by Cataloguer
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بررسی اثر ضد درد تریفلوپرازین به عنوان مهارکننده کالموجولین
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