PubMed Health⌕ Search

PubMed · 8375429

Progress note on Japanese multicenter bromocriptine monotherapy.

Abstract

The nationwide multicenter collaborative study for evaluating the monotherapy of Parkinson's disease with bromocriptine for a period of 5 years from 1986 was reviewed last year. The present report summarizes the follow-up in its 6th year: it includes 30 patients with Parkinson's disease who continued to receive bromocriptine monotherapy for 6 years and 66 patients who received bromocriptine-levodopa combination therapy during the same period. The mean daily dose of bromocriptine in the 6th year was about the same in the two groups (11.9 and 12.2 mg). In terms of Hoehn-Yahr's severity grade, severity increased in 20% of the patients undergoing bromocriptine monotherapy, whereas of the patients in the bromocriptine-levodopa combination group it was 45%. Wearing-off phenomenon was not seen in the bromocriptine monotherapy group. By contrast, 30% of the patients in the combination therapy group manifested this phenomenon which, when it occurred, invariably followed the administration of levodopa. Absence of the wearing-off phenomenon implies that bromocriptine has a direct protective action on degenerating substantia nigra.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

S Kuno. 1993. Progress note on Japanese multicenter bromocriptine monotherapy.. https://doi.org/10.1159/000118532

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Conformational heterogeneity of cytochrome P450 3A4 revealed by high pressure spectroscopy.

We applied hydrostatic pressure perturbation to study substrate-induced transitions in human cytochrome P450 3A4 (CYP3A4) with bromocriptine (BCT) as a substrate. The barotropic behavior of the purified enzyme in solution was compared with that observed in recombinant microsomes of Saccharomyces cerevisiae coexpressing CYP3A4, cytochrome b(5), (b(5)) and NADPH-cytochrome P450 reductase (CPR). Important barotropic heterogeneity of CYP3A4 was detected in both cases. Only about 70% of CYP3A4 in solution and about 50% of the microsomal enzyme were susceptible to a pressure-induced P450-->P420 transition. The results suggest that both in solution and in the membrane CYP3A4 is represented by two conformers with different positions of spin equilibrium and different barotropic properties. No interconversion between these conformers was observed within the time frame of the experiment. Importantly, a pressure-induced spin shift, which is characteristic of all cytochromes P450 studied to date, was detected in CYP3A4 in solution only; the P450-->P420 transition was the sole pressure-induced process detected in microsomes. This fact suggests unusual stabilization of the high-spin state of CYP3A4, which is assumed to reflect decreased water accessibility of the heme moiety due to specific interactions of the hemoprotein with the protein partners (b(5) and CPR) and/or membrane lipids.

Bromocriptine↗

Dopamine resistance of prolactinomas.

Resistance to dopamine agonists can be defined with respect to failure to normalize PRL levels and failure to decrease tumor size by > or = 50%. Using these definitions, failure to normalize PRL levels is seen in 24% of those treated with bromocriptine, 13% of those treated with pergolide and 11% of those treated with cabergoline. Failure to achieve at least a 50% reduction in tumor size occurs in about one-third of those treated with bromocriptine and 10-15% of those treated with pergolide or cabergoline. Studies of in vitro cell preparations show that the D2 receptors of resistant tumors are decreased in number but have normal affinity. Treatment approaches for resistant patients include switching to another dopamine agonist and raising the dose of the drug as long as there is continued response to the dose increases and no adverse effects. Transsphenoidal surgery can also be done. If fertility is desired, clomiphene, gonadotropins, and GnRH are also options. If fertility is not desired, estrogen replacement may be used unless there is a macroadenoma, in which case control of tumor growth is also an issue and dopamine agonists are generally necessary. However, in many cases modest or even no reduction may be acceptable long-term as long as there is not tumor growth. Hormone replacement (estrogen or testosterone) may cause a decrease in efficacy of the dopamine agonist so that it must be carried out cautiously. Reduction of endogenous estrogen, use of selective estrogen receptor modulators, and aromatase inhibitors are potential experimental approaches.

Bromocriptine↗