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Abstract

Effects of the antiparkinsonian drug budipine on neurotransmitter release in central nervous system tissue in vitro.

R Jackisch, H Y Huang, W Reimann and N Limberger
Journal of Pharmacology and Experimental Therapeutics February 1993, 264 (2) 889-898;
R Jackisch
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H Y Huang
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W Reimann
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N Limberger
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Abstract

The effects of the antiparkinsonian drugs budipine and biperiden on spontaneous and electrically evoked release of dopamine (DA), acetylcholine (ACh), GABA or noradrenaline (NA) were studied in caudate nucleus or cortex slices, respectively, of the rabbit brain. Whereas both drugs (1-10 microM) strongly increased spontaneous [3H]outflow in caudate nucleus slices preincubated with [3H]DA, budipine inhibited but biperiden facilitated the evoked DA release. In the presence of the DA-reuptake inhibitor nomifensine, a significant part of the budipine-induced basal [3H] outflow consisted of unmetabolized DA. Synaptosomal high-affinity uptake of [3H]DA was only weakly affected by budipine and biperiden (IC50 values, 11 and 9 microM, respectively). Budipine enhanced also basal [3H]outflow from cortex slices prelabeled with [3H]NA, however this outflow consisted mainly of NA metabolites even in the presence of cocaine. The evoked release of [3H]ACh in rabbit caudate nucleus slices preincubated with [3H] choline was almost unaffected by budipine but enhanced by biperiden in the absence of further drugs. In the presence of nomifensine, however, budipine inhibited, but biperiden still enhanced, the evoked ACh release. Moreover, both drugs showed antimuscarinic properties in the presence of the ACh esterase inhibitor physostigmine, i.e., they facilitated the evoked ACh release, exhibiting pA2 values of about 6.9 (budipine) and 8.3 (biperiden). Addition of the D2 receptor antagonist domperidone diminished all inhibitory effects of budipine on the evoked ACh release. The evoked overflow of [3H] in caudate nucleus slices preincubated with [3H]GABA was reduced by both budipine and biperiden. It is concluded that both anticholinergic and indirect dopaminomimetic properties contribute to the antiparkinsonian effects of budipine, whereas biperiden exhibits mainly anticholinergic effects. Moreover, both drugs might disinhibit GABA controlled neurons in the central nervous system.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 264, Issue 2
1 Feb 1993
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Abstract

Effects of the antiparkinsonian drug budipine on neurotransmitter release in central nervous system tissue in vitro.

R Jackisch, H Y Huang, W Reimann and N Limberger
Journal of Pharmacology and Experimental Therapeutics February 1, 1993, 264 (2) 889-898;

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Abstract

Effects of the antiparkinsonian drug budipine on neurotransmitter release in central nervous system tissue in vitro.

R Jackisch, H Y Huang, W Reimann and N Limberger
Journal of Pharmacology and Experimental Therapeutics February 1, 1993, 264 (2) 889-898;
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