Effects of the antiparkinsonian drug budipine on central neurotransmitter systems
Identifieur interne : 002100 ( Main/Exploration ); précédent : 002099; suivant : 002101Effects of the antiparkinsonian drug budipine on central neurotransmitter systems
Auteurs : Thomas Klockgether [Allemagne] ; Ullrich Wüllner [Allemagne] ; Joachim Peter Steinbach [Allemagne] ; Vibke Petersen [Danemark] ; Lechoslaw Turski [Allemagne] ; Peter-Andreas Löschmann [Allemagne]Source :
- European Journal of Pharmacology [ 0014-2999 ] ; 1996.
Abstract
Budipine is a novel antiparkinsonian drug which is particularly beneficial in the treatment of parkinsonian tremor. The mechanism of action of budipine is not fully understood. To study whether budipine has dopaminergic activity in vivo, we used the 6-hydroxydopamine rotational model of Parkinson's disease. Budipine (0.78–12.5 mg/kg i.p.) did not induce ipsilateral or contralateral rotations, suggesting that it does not possess direct or indirect dopaminergic activity. This conclusion is further supported by the observation that budipine (10 mg/kg) i.v. did not facilitate striatal dopamine release measured in vivo by brain microdialysis. To investigatate possible antimuscarinic and N-methyl-D-aspartic acid (NMDA) antagonistic properties of budipine, we compared budipine with the antimuscarinic antiparkinsonian drug biperiden and the NMDA receptor antagonist 3-[(±)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (CPP). In receptorbinding assays, budipine inhibited thienylcyclohexylpiperidyl-3,4-[3H](n) ([3H]TCP) (2.5 nM)-binding with an IC50 of 36 μM and [3H]3-quinuclidinol benzilate-binding with an IC50 of 1.1 μM. The respective values for biperiden were 170 and 0.053 μM. In line with these findings, budipine and CPP increased the threshold for NMDA-induced seizures in mice with an ED50 of 10.2 and 4.4 mg/kg, respectively, whereas biperiden was not effective. In 6-hydroxydopamine-lesioned rats, budipine (3.13–12.5 mg/kg) and CPP (0.1–0.39 mg/kg) increased the number of contralateral rotations induced by apomorphine, whereas biperiden was not effective. The present data suggest that budipine acts by blocking muscarinic and NMDA transmission while facilitation of dopaminergic transmission does not appear to contribute to its in vivo action. In comparison to biperiden, which has also antimuscarinic and NMDA receptor antagonistic properties, the anti-NMDA action of budipine is more prominent.
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DOI: 10.1016/0014-2999(96)00046-5
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The mechanism of action of budipine is not fully understood. To study whether budipine has dopaminergic activity in vivo, we used the 6-hydroxydopamine rotational model of Parkinson's disease. Budipine (0.78–12.5 mg/kg i.p.) did not induce ipsilateral or contralateral rotations, suggesting that it does not possess direct or indirect dopaminergic activity. This conclusion is further supported by the observation that budipine (10 mg/kg) i.v. did not facilitate striatal dopamine release measured in vivo by brain microdialysis. To investigatate possible antimuscarinic and N-methyl-D-aspartic acid (NMDA) antagonistic properties of budipine, we compared budipine with the antimuscarinic antiparkinsonian drug biperiden and the NMDA receptor antagonist 3-[(±)-2-carboxypiperazine-4-yl]-propyl-1-phosphonic acid (CPP). In receptorbinding assays, budipine inhibited thienylcyclohexylpiperidyl-3,4-[3H](n) ([3H]TCP) (2.5 nM)-binding with an IC50 of 36 μM and [3H]3-quinuclidinol benzilate-binding with an IC50 of 1.1 μM. The respective values for biperiden were 170 and 0.053 μM. In line with these findings, budipine and CPP increased the threshold for NMDA-induced seizures in mice with an ED50 of 10.2 and 4.4 mg/kg, respectively, whereas biperiden was not effective. In 6-hydroxydopamine-lesioned rats, budipine (3.13–12.5 mg/kg) and CPP (0.1–0.39 mg/kg) increased the number of contralateral rotations induced by apomorphine, whereas biperiden was not effective. The present data suggest that budipine acts by blocking muscarinic and NMDA transmission while facilitation of dopaminergic transmission does not appear to contribute to its in vivo action. In comparison to biperiden, which has also antimuscarinic and NMDA receptor antagonistic properties, the anti-NMDA action of budipine is more prominent.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Danemark</li></country><region><li>Bade-Wurtemberg</li><li>Berlin</li><li>District de Tübingen</li></region><settlement><li>Berlin</li><li>Tübingen</li></settlement></list><tree><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Klockgether, Thomas" sort="Klockgether, Thomas" uniqKey="Klockgether T" first="Thomas" last="Klockgether">Thomas Klockgether</name></region><name sortKey="Loschmann, Peter Andreas" sort="Loschmann, Peter Andreas" uniqKey="Loschmann P" first="Peter-Andreas" last="Löschmann">Peter-Andreas Löschmann</name><name sortKey="Steinbach, Joachim Peter" sort="Steinbach, Joachim Peter" uniqKey="Steinbach J" first="Joachim Peter" last="Steinbach">Joachim Peter Steinbach</name><name sortKey="Turski, Lechoslaw" sort="Turski, Lechoslaw" uniqKey="Turski L" first="Lechoslaw" last="Turski">Lechoslaw Turski</name><name sortKey="Wullner, Ullrich" sort="Wullner, Ullrich" uniqKey="Wullner U" first="Ullrich" last="Wüllner">Ullrich Wüllner</name></country><country name="Danemark"><noRegion><name sortKey="Petersen, Vibke" sort="Petersen, Vibke" uniqKey="Petersen V" first="Vibke" last="Petersen">Vibke Petersen</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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