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This publication is protected and can be accessed only from certain IPs.

Title: Investigation of [gamma]-butyrolactone derivatives' analgesic activity

Abstract:

The aim of the present studies was the evaluation of the analgesic activity of some 3-substituted γ-butyrolactone derivatives and their amide counterparts. Some of the experiments aimed to elucidate the mechanism of analgesic activity of the investigated compounds. In the introductory part of the dissertation thesis the nociceptive process was described. The modulatory role of transmitters ( e.g. excitatory ammo acids, substance P, prostanoids, ATP, GABA, opioids) and ion channels was discussed, as well. In the experimental part study design and obtained results were described and precisely discussed. The screening tests included the activity of the investigated substances m acute (hot plate, writhing and capsaicin-induced) and tonic pain models in mice. Spontaneous locomotor activity and acute toxicity were assessed, too. The most active compounds were additionally tested in guinea pigs for their local anaesthetic activity (infiltration and corneal anaesthesia) Moreover two most active lactones were tested for their interaction with serotonergic, glutamatergic and endocannabinoid systems. On the basis of the experiments it was established that 3-substituted phenylpiperazine derivatives of γ-butyrolactone are highly antinociceptive and this effect is not a consequence of their receptor affinity (GABAergic type A, B, adrenergic α2, opioidergic μ or serotonergic 5HT1A). Neither d ; oes it derive from their inhibitory effect on the proinflammatory and algesic prostaglandin E2synthesis. The part of the studies concerned the mechanism of analgesic activity of LPP1, i.e. the most active compound. It was established that the primary afferent unmyelinated C-fibres transmitting painful stimuli towards the central nervous system are the probable site of its action The influence on the peripheral or central glutamatergic system and voltage-gated ion channels (sodium or calcium) is taken into account, as well. lt seems that the mechanism of LPP1's antinociceptive activity resembles the activity of co-analgesic drugs, namely the antiepileptic or local-anaesthetic drugs. Amide analogues of the investigated lactones seem to lose their analgesic and local anaesthetic activities. Simultaneously, the locomotor activity is affected, too - the amide derivatives seem to increase it, which suggests their excitatory properties.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

farmacja

Degree grantor:

Wydział Farmaceutyczny

Promoter:

Filipek, Barbara

Date issued:

2009

Identifier:

oai:dl.cm-uj.krakow.pl:775

Call number:

ZB-111784

Language:

pol

Access rights:

tylko w bibliotece

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Last modified:

Jun 21, 2023

In our library since:

Nov 21, 2012

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11

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0

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/775

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