Bromocriptine in Parkinson disease.
Bromocriptine is an ergopeptine derivative and dopamine agonist that predominantly stimulates the striatal D2 non-adenyl cyclase-linked dopamine receptors. Bromocriptine, unlike other dopamine agonists, has mixed "agonist-antagonist" properties at these receptors. The striatal dopamine receptors exist in two different affinity states: a low and a high affinity state. Bromocriptine, unlike other dopamine agonists, does not differentiate between the low and the high affinity state of the D2 receptors, and bromocriptine does not induce a conformational change in these receptors. Bromocriptine, in low doses, is effective in patients with mild to moderate Parkinson's disease, while bromocriptine in higher doses is needed in patients with advanced disease. Both in low doses and in high doses, bromocriptine combined with levodopa is usually more effective than bromocriptine alone. The efficacy of low dose (5-30 mg/day) and high dose (31-100 mg/day) bromocriptine alone and with levodopa was examined in 27 studies encompassing 790 patients. Forty-six % of the studies were done in a double blind manner. In four studies of 79 patients, low dose bromocriptine (16 mg/day) without levodopa resulted in improvement in 58% of the patients. Only 9% of the patients experienced adverse effects. Most of the patients (63%) and mild or moderate Parkinson disease. In seven studies of 143 patients, high dose bromocriptine (56 mg/day) without levodopa resulted in improvement in 62% of patients, but with 27% having adverse effects. Most of these patients (77%) had mild or moderate disease. Diurnal oscillations in performance, the "wearing off" or "on-off" effect, were not seen during treatment with bromocriptine alone. In nine studies of 201 patients, low dose bromocriptine (23 mg/day) and levodopa resulted in improvement in 71% of patients with 26% having adverse effects. Most of these patients (66%) had advanced disease, and many had diurnal oscillations in performance. In seven studies of 367 patients, high dose bromocriptine (48 mg/day) and levodopa resulted in improvement in 58% with 37% having adverse effects. Most of these patients (85%) had advanced disease. The increased effectiveness of bromocriptine in combination with levodopa may be explained as follows. Bromocriptine by itself does not discriminate between the low and the high affinity states of the dopamine receptors.(ABSTRACT TRUNCATED AT 400 WORDS)
D000368:Aged; D000818:Animals; D001971:Bromocriptine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004873:Ergolines / Q000627:therapeutic use; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use; D008090:Lisuride / Q000627:therapeutic use; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy*; D010479:Pergolide; D013997:Time Factors
D004873:Ergolines; D010479:Pergolide; D001971:Bromocriptine; D007980:Levodopa; D008090:Lisuride