Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
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Advances in Clinical and Experimental Medicine

2010, vol. 19, nr 1, January-February, p. 21–31

Publication type: original article

Language: English

Biological Peculiarities of the Analgesic Drug Nefopam in Rats

Biologiczne właściwości nefopamu – leku przeciwbólowego u szczurów

Magdalena Beśka1,, Izabela Walawender1,, Jacek Kasperski2,, Dariusz Skaba3,, Przemysław Nowak1,, Edyta Reichman-Warmusz4,, Ryszard Szkilnik1,

1 Department of Pharmacology, Medical University of Silesia, Zabrze, Poland

2 Department of Prosthetic Dentistry, Medical University of Silesia, Zabrze, Poland

3 Department of Conservative Dentistry and Endodontics Division of Dental Propedeutics, Medical University of Silesia, Zabrze, Poland

4 Department of Histology, Medical University of Silesia, Zabrze, Poland

Abstract

Background. It is well known that besides the typical symptoms of Parkinson’s disease, non-motor disabilities were found to be major contributing factors to impairments in disease-related quality of life. The scope of the non-motor manifestations of Parkinson’s disease is broad and includes depression, pain, disturbances in mood, cognition, autonomic function, sleep, perceptual changes, and impulse control. Pain as a primary symptom is usually located on the side of the body that is most compromised by the disease. The treatment always demands a great adjustment of dopamine agonist, local injections of steroids, massages, physiotherapy, and analgesic therapy, which improve the life quality of patients.
Objectives. The aim of this study was to examine the biological effects of nefopam, a non-opioid analgesic drug, in rats.
Material and Methods. Locomotor activity, stereotypy, catalepsy, depressive behavior, and motor coordination were examined in adult male Wistar rats after nefopam administration. Furthermore, the dopamine (DA) synthesis rate in the frontal cortex, nucleus accumbens, and striatum after nefopam challenge was determined and microdialysis of the striatum was performed.
Results. Nefopam administered in doses of 1, 5, 10, 20, and 40 mg/kg i.p. was without effect on locomotor activity in the rats, although higher doses (20 or 40 mg/kg i.p.) evoked behavioral stereotypy. Nefopam ameliorated motor coordination (assessed with the rotarod test) and diminished the cataleptogenic effect of SCH 23390. In biochemical studies it was shown that nefopam reduced the DA synthesis rate in the frontal cortex, nucleus accumbens and striatum and augmented DA release in the striatum in rats.
Conclusion. These data lead to the proposal that the “behavioral-biochemical profile” of this analgesic justifies its use in patients with motor abnormalities, for example in Parkinson’s disease.

Streszczenie

Wprowadzenie. Wiadomo, że typowym motorycznym objawom choroby Parkinsona towarzyszą inne zaburzenia, które znacznie pogarszają jakość życia pacjentów z tym schorzeniem. Zalicza się do nich depresję, ból, pogorszenie funkcji kognitywnych, zaburzenia snu oraz objawy pochodzące z układu autonomicznego. Spośród wymienionych, ból jest jedną z najczęstszych skarg tych pacjentów. Leczenie wymaga najczęściej korekty dawek stosowanych już agonistów dopaminowych, miejscowych iniekcji kortykosteroidów, masaży, fizykoterapii oraz podawania leków przeciwbólowych.
Cel pracy. Uzyskanie odpowiedzi, czy nefopam – nieopioidowy analgetyk wykazuje inne, oprócz przeciwbólowych, właściwości biologiczne u szczurów.
Materiał i metody. U dorosłych szczurów samców szczepu Wistar zbadano aktywność lokomotoryczną z oceną stereotypii, katalepsję, badanie działania przeciwdepresyjnego oraz koordynację ruchową po podaniu nefopamu w różnych dawkach. Dokonano ponadto oceny szybkości syntezy dopaminy (DA) w korze czołowej, jądrze półleżącym przegrody i prążkowiu po podaniu badanego leku oraz wykonano badanie mikrodializy prążkowia.
Wyniki. Nefopam stosowany w dawkach 1,0; 5,0; 10; 20 oraz 40 mg/kg i.p. (dootrzewnowo) nie wpływał na aktywność lokomotoryczną badanych szczurów. Po podaniu większych dawek (20 lub 40 mg/kg i.p.) obserwowano u zwierząt zachowanie stereotypowe. Nefopam poprawiał natomiast kordynację ruchową (w teście rota-rod) oraz osłabiał kataleptogenne działanie SCH 23390. W badaniach biochemicznych wykazano, że badany lek zmniejszał szybkość syntezy DA w korze czołowej, jądrze półleżącym przegrody oraz prążkowiu, nasilał także uwalnianie DA w prążkowiu u szczurów.
Wnioski. Na podstawie przeprowadzonych badań należy stwierdzić, że „behawioralno-biochemiczny profil” badanego analgetyku przemawia za tym, że może on być z dużym bezpieczeństwem stosowany u osób z zaburzeniami funkcji motorycznych, np. w chorobie Parkinsona.

Key words

nefopam, locomotor activity, motor coordination, catalepsy, dopamine, rats

Słowa kluczowe

nefopam, aktywność lokomotoryczna, koordynacja ruchowa, katalepsja, dopamina, szczury

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