title: MK 458, a selective and potent D2 receptor agonist in advanced Parkinson's disease.
abstract: MK 458 is a potent and selective D2 receptor agonist. MK 458 consists of (+)-4-propyl-9-hydroxynaphthoxazine (PHNO) in a hydroxypropyl-methylcellulose-lactose matrix. MK 458, mean dose 8.1 mg (range 2.5 to 13.5 mg), was administered to 14 patients with advanced Parkinson's disease (PD) who were no longer satisfactorily responding to levodopa. The duration of the study was 4 weeks with a titration to maximum dose in 2 weeks. The addition of MK 458 resulted in a mean reduction in levodopa of 41% (range 0 to 81%). This degree of levodopa reduction was not seen in previous studies with other DA agonists. While the reduction in signs of PD was comparable to those on levodopa, MK 458 did not induce dyskinesias or dystonias. It is postulated that MK 458 may be able to replace levodopa as the primary treatment for PD.
mesh_terms: D000328:Adult; D000368:Aged; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002230:Carbidopa / Q000627:therapeutic use; D015259:Dopamine Agents / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D065347:Hypromellose Derivatives; D007785:Lactose / Q000008:administration & dosage / Q000627:therapeutic use*; D007980:Levodopa / Q000627:therapeutic use; D008090:Lisuride / Q000627:therapeutic use; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010078:Oxazines / Q000008:administration & dosage / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology; D010479:Pergolide / Q000627:therapeutic use; D011597:Psychomotor Performance / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*
chemical_list: D000978:Antiparkinson Agents; D015259:Dopamine Agents; D010078:Oxazines; D011954:Receptors, Dopamine; C042631:naxagolide; D010479:Pergolide; D065347:Hypromellose Derivatives; D007980:Levodopa; D008747:Methylcellulose; D008090:Lisuride; D007785:Lactose; D002230:Carbidopa