Bromocriptine, structure

Figure 6. Structural Positions (bold numbers) in the Bromocriptine Skeleton and corresponding C-13-NMR Chemical Shifts ( in italics) in ppm downfield...

X-ray structural analysis of bromocriptine, crystallized as the base from dichloromethane/diethylether, has been carried out on a CAD 4-diffractometer with CuKa-radiation (16). 3371 reflexions were within sin G/A<0.62 A. Assessment of the structure was achieved by computation to a refinement of R = 0.033 for the absolute configuration. 

The principal metabolites have been isolated from the bile of rats treated with high doses of bromocriptine. The structure of the isolated metabolites was elucidated by means of spectroscopic techniques. 

DA receptors are classified as D1 to D5. Bromocriptine and pergolide act as agonists at certain subtypes, and neuroleptics such as haloperidol and thorazine act as antagonists. It is produced by several nuclei in the brain, but most notably the substantia nigra and the ventral tegmental area (VTA) of the midbrain. The substantia nigra mainly projects to the basal ganglia and the VTA supplies limbic and cortical structures. 

Bromocriptine is a D2 agonist its structure is shown in Table 16-6. This drug has been widely used to treat Parkinson s disease in the past, but is now rarely used for this purpose, having been superseded by the newer dopamine agonists. Bromocriptine is absorbed to a variable extent from the gastrointestinal tract peak plasma levels are reached within 1-2 hours after an oral dose. It is excreted in the bile and feces. The usual daily dose of bromocriptine for parkinsonism varies between 7.5 and 30 mg. To minimize adverse effects, the dose is built up slowly over 2 or 3 months from a starting level of 1.25 mg twice daily after meals the daily dose is then increased by 2.5 mg every 2 weeks, depending on the response or the development of adverse reactions. 

Recent data in our laboratories indicated the possible involvement of central and peripheral dopamine binding sites in the pathogenesis of duodenal ulceration. Structure activity studies with duodenal ulcerogens implicated dopamine as a putative mediator and/or modulator in duodenal ulceration. Using the cysteamine- or propionitrile-induced duodenal ulcer model in rats, we found that dopamine agonists (e.g., bromocriptine, lergotrile,... 

Retroperitoneal fibrosis (SEDA-12, 123) (18) and pulmonary fibrosis (SEDA-11, 130) during treatment with high doses of bromocriptine have been observed. The drug s structural relation to methysergide clearly has to be kept in mind. Pleural thickening and effusions can be present in up to 6% of patients treated with bromocriptine for Parkinson s disease, and this is related to duration of exposure and cumulative dose (19). The author recommended drug withdrawal in these patients. However, withdrawal does not always lead to complete resolution of the lesions (20). 

Chart 1.8 Chemical structures of bromocriptine (15), ABT-431 (16), dihydrexidine (17), ropinirole... 

Elaborations of the ergoline structural lead were prevailingly addressed to the development of new antiparkinsonian agents, since bromocriptine, acting as a D2 agonist, had... 

Oda T, Kume T, Izumi Y, Takada-Takatori Y, Niidome T, Akaike A (2008) Bromocriptine, a dopamine D2 receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC 12 cells. Eur J Pharmacol 598 27-31... 

Camerman, N., Chan, L.Y.Y. and Camerman, A. (1979) Stereochemical characteristic of dopamine agonists Molecular structure of bromocriptine and structural comparisons with apomorphine. Mol Pharmacol, 16, 729-736. 

FIGURE 11.8. Structures selected dopamine receptor agonists (a) Bromocriptine, (b) Lisuride, (c) Piribedil, and (d) Ropinirole [52-55]. 

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