PubMed · 10778103
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M Yoshimura, Y Habuchi, H Tanaka. 1999. [Dopamine].. https://pubmed.ncbi.nlm.nih.gov/10778103/
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Alcohol potentiation of 5-HT3 receptors was examined in NCB-20 neuroblastoma cells using whole-cell patch-clamp electrophysiological techniques. Activation of the receptor with the weak partial agonist dopamine (DA) was used to examine alcohol effects under conditions of full agonist occupancy, but low probability of channel opening. Dopamine activation of the receptor increased in a concentration-dependent manner (EC50=0.28 mM), and on average maximal responses to DA were 8.0+/-0.8% of the maximal response to 5-HT. Ethanol (EtOH) and trichloroethanol (TCEt) potentiated DA-activated ion current mediated by 5-HT3 receptors. Potentiation of responses to a maximally effective dopamine concentration averaged 52.0+/-8.0% for EtOH and 567+/-43% for TCEt, which was comparable to the potentiation observed when receptors were activated by a low concentration of 5-HT. The alcohols increased both the potency and efficacy with which dopamine activated the receptor. The observation that alcohols increase the maximal efficacy of dopamine activation of the receptor indicates that one action of alcohols on the 5-HT3 receptor is to increase the probability of channel opening independent of any effect on agonist affinity.
Dopamine determination in pharmaceutical preparations based on its oxidation with periodate (IO(4)(-)) using a new IO(4)(-)-selective electrode under flow conditions is presented. An electrode with a tubular configuration, no internal reference solution, and a PVC (31. 2%) membrane, with metaperiodate bis(triphenylphosphoranylidene)ammonium (1.3%) as ion exchanger and 2-nitrophenyloctylether (67.5%) as mediator solvent, was used. Optimization procedures were directed at potentials versus dopamine readings instead of potential versus the remaining IO(4)(-). This approach was achieved by selecting a 50-cm reactor and an overall flow of 7 mL/min, and injecting 70 microL of dopamine standards in a 3.0 x 10(-4) M IO(4)(-) solution. Under these conditions, a linearity range of 8.0 x 10(-3) to 2.7 x 10(-1) g/L, with a slope of 310.1 +/- 7.4 mV L g(-1) and a reproducibility of +/-0.4 mV, were recorded (n = 8). Interference from common excipients was negligible. Under these conditions, analysis of dopamine injections (n = 12) presenting 200 mg/injection gave average and standard deviation values of 201.0 and 3.3 mg/injection, respectively. A simple and inexpensive flow-injection analysis (FIA) manifold, with a good potentiometric detector, enabled the analysis of 200 samples/h without requiring pretreatment procedures. Comparison with the dopamine injection analysis in the United States Pharmacopoeia monograph showed good accuracy, with a relative deviation of -0.2%.
Parkinson's disease no longer seems to be a disease entity caused by only one pathogenetic factor. The facile characterization of Parkinson's disease as a more or less isolated disorder of the dopaminergic system proves to be an unacceptable oversimplification of the pathology of the disease. Characteristically, not all dopaminergic systems of the central nervous system are involved in the degenerative process. In addition to the nigrostriatal dopaminergic pathway, parts of the glutamatergic, cholinergic, tryptaminergic, noradrenergic, adrenergic, serotonergic, and peptidergic neurons show serious cytoskeletal damage. In the light of these findings, drugs influencing these transmitter systems should be useful in the treatment of parkinsonian symptoms. For this reason, non-dopaminergic drugs are gaining more and more importance. Besides the theoretically interesting adenosine A2 receptor antagonists, budipine, a polyvalent potent new antiparkinsonian drug, has been tested in clinical studies. Budipine is a potent non-dopaminergic antiparkinsonian drug with pharmacological effects that are not comparable to those of conventional drugs applied in Parkinsonian pharmacotherapy. Budipine experimentally increased the brain content of noradrenaline, dopamine, serotonin, and histamine. The dopamine, serotonin, noradrenaline, gamma aminobutyric acid (GABA), and endorphine receptor affinities were not altered, but N-methyl-D-aspartate (NMDA) and sigma receptor affinities were increased as shown by in vivo and in vitro trials with budipine. MPTP (N-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine) and MPP+ antagonistic effects have also been demonstrated. Budipine also shows neuroprotective as well as symptomatic antiparkinsonian effects. In two randomized, double-blind, multicenter, placebo-controlled studies, relevant therapeutic effects have been observed in previously untreated, so-called "de-novo" parkinsonian patients and in subjects in later stages of the disease. Budipine significantly reduces akinesia, rigidity, and tremor. Optimal effects of budipine can be seen 4-6 weeks after starting treatment with this substance. Budipine can be added to all available antiparkinsonian drugs. An open, prospective, long-term study of 2532 patients with Parkinson's disease (Study BY701/01A) confirmed the favorable safety and tolerability profiles of budipine.