Bromocriptin

Bromo pyruvaldoxime Methotrexate N-Bromosuccinimide Betamethasone acetate Bromocriptine Medrogestone 2-Bromothiophene Thihexinol... 

Epoxypropyl)-2-methyl-5-nitroimidazole Ornidazole Ergocryptine Bromocriptine Erythromycin... 

Parkinsonian patients receiving the dopamine precursor, levodopa or dopamine receptor agonists, such as bromocriptine and apomoiphine may experience nausea and vomiting due to stimulation of dopamine D2 receptors in the CTZ. 

Today, 2-bromo-a-ergocryptine (bromocriptine) is the second (after dihydroergotoxine) most extensively used compound from the group of ergot alkaloids. 

Table I. Comparison of brominating methods of preparation of bromocriptine 2... 

The well know isomerisation (ref. 11) at the position 8 in ergolene nucleus is usually easy and is difficult to be totally avoided. The moderate acidic media, lowering of temperature and non-polar solvents can successfully suppress this reaction. At any case, the iso compound 2-bromo-a-ergocryptinine 2a can readily be transformed back into bromocriptine 2, also in industrial scale. 

In the first step bromocriptine 2 is isomerized to 2a, followed by an attack on proline ring in aminocyclol moiety of the molecule (formation of a new double bound on lO -ll, and bromination). This dibromo-compound 5 is brominated additionally on C-2 -propyl group. Tribromo-compound fi is very lipophilic and practically devoid of pharmacological activity. Hydroxy group and amide groups remain intact after all these reactions. 

Transformation of bromocriptine free base 2 into water soluble salt -mesylate, is the only way to obtain a suitable therapeutical form. Crystallization of mesylate using alcohol as a solvent in the presence of excess of strong acid, e.g. methanesulphonic acid can induce formation of 12 -0-alkyl-derivative 2. Until now this derivatisation of ergot molecule has been practically unknown. In continuation we developed the preparative method for obtaining these compounds, (using tetrafluoroboric acid as a catalyst) (ref. 20). 

Mother liquors from the production of bromocriptine 2 were dried by evaporation under vacuum. The dry residue (82.2 g) was applied on chromatographic column (I.D. = 3 cm, lenght = 20 cm) packed with silicagel 60, granulation 0.063 - 0.040 mm and eluted by flash - chromatography with pure dichloromethane. Two separate fractions were obtained and crystallized from dichloromethane (- 15°C). 

Bromocriptine 2 (0.65 g, 1 mmol) was dissolved in 100 ml of dry ethanol and 60 ml of tetrafluoroboric acid / diethylether complex (85 %) was added while stirring. After standing overnight at RT the solvent was evaporated and the raw product isolated by extraction in the system dichloromethane 12% ammonia in water and evaporated to the dry residue. This residue was applied to the chromatographic column (I.D. = 2 cm, lenght = 20 cm) packed with silicagel and eluted with dichloromethane / ethylacetate =1 1. The fractions containing 2 were evaporated to the dry residue and crystallized from alcohol. 

Amantidine, bromocriptine, mazindol, pergolide, cabergoline, L-dopa/carbidopa, pramipexole, ABT-431, catecholamine metabolism inhibitors (disulfiram, phenelzine, selegiline), amineptine Methylphenidate, /-amphetamine, tropanes, GBR-12909 (partial agonist that may also act as antagonist), modafinil, coca tea... 

Because chronic cocaine use appears to reduce the efficiency of central dopamine neurotransmission, a number of dopaminergic compounds, including amantadine, bromocriptine, mazindol, and methylphenidate, have been examined as treatments for cocaine abuse. It is thought that these relatively slow-onset dopaminergic agents, with low or relatively low abuse potential, would correct the dopamine dysregulation and alleviate withdrawal symptoms following chronic stimulant use. 

Note Separate potassium iodide and starch solutions can also be used successively [2], The detection limits for bromureides are 40 to 200 ng substance per chromatogram zone [7, 10]. Bromopride, bromazepam, bromhexine and bromocriptine do not reac [10]. 

Bromisoval (h/ f 15-20) yielded dark brown chromatogram zones on a light brown background. Bromopride, bromazepam, bromhexine, bromocriptine, caryophyllene epoxide and rose oxide did not react. 

DA agonists — bromocriptine, apomorphine and ADTN decrease release. 

Those for the D2 receptor (e.g. bromocriptine) have a particular value in the treatment of Parkinson s disease by reproducing the effects of the dopamine lost through degeneration of the nigrostriatal tract (Chapter 15). They are also used to reduce the undesirable effects of prolactinaemia (high plasma prolactin), such as amenorrhoea and galactorrhoea. 

Another indication of the importance of DA in motor control is the observation that in humans its precursor levodopa, and DA agonists like bromocriptine, not only overcome the akinesia of Parkinsonism but in excess will actually cause involuntary movements, or dyskinesia (Chapter 14). Also it is well known that DA antagonists like chlorpromazine and haloperidol produce Parkinsonian-like symptoms in humans (and catalepsy in animals) and, as indicated above, reduce the dyskinesia of Huntington s Chorea. Thus DA seems to sit on a knife edge in the control of motor function (Fig. 7.8). 

Opioids, benzodiazepines, barbiturates, corticosteroids, dopamine agonists (e.g., amantadine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole), H2-receptor antagonists, anticholinergics (e.g., diphenhydramine, trihexylphenidyl), P-adrenergic blockers, clonidine, methyldopa, carbamazepine, phenytoin, baclofen, cyclobenzaprine, lithium, antidepressants (e.g., tricyclic antidepressants, selective serotonin reuptake inhibitors), and interleukin-2... 

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