Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0013421 (dystonia)
 8,418 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Eight Cebus apella monkeys were treated with haloperidol for 2 years. Five monkeys had developed mild oral tardive dyskinesia and all were primed for neuroleptic induced dystonia, thus serving as a model for both chronic and acute extrapyramidal side effects. In this model, the partial dopamine D2 receptor agonists SDZ HDC-912, SDZ HAC-911, terguride, (-)-3-(3-hydroxyphenyl)-N-propylpiperidine) ((-)-3-PPP) and SND 919 were tested for extrapyramidal side-effect liability. Their antipsychotic potential was also tested, using a dose of dextroamphetamine producing mild stereotypy and moderate motoric unrest. For comparison, the dopamine D2 receptor agonist, LY 171555 and antagonist, raclopride were used. In contrast to the other drugs tested, SDZ HAC-911 consistently reduced oral activity, P < 0.05 (at doses from 0.005 to 0.025 mg/kg). The relative dystonic potencies were raclopride > SDZ HDC-912 > SDZ HAC-911 = terguride. Neither (-)-3-PPP nor SND 919 produced dystonia, but had observable dopamine D2 receptor agonistic effects, (-)-3-PPP producing emesis at 1-4 mg/kg and SND 919 producing motoric unrest and stereotypy at 0.05-0.25 mg/kg. Comparing the antiamphetamine effects of the more antagonist-like drugs with raclopride, the relative potencies were terguride = SDZ HAC-911 > SDZ HDC-912 > raclopride. Comparing the antiamphetamine effects of the more agonist-like drugs with LY 171555, the relative potencies were SND 919 > (-)-3-PPP > LY 171555 in relation to motoric unrest, while neither (-)-3-PPP nor LY 171555 produced inhibition of stereotypy.
 ...
PMID:Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol. 810 65

Forty-one patients with Parkinson's disease and severe dyskinesias were analyzed retrospectively to determine if some general principles would emerge to aid physicians handling this complication of treatment. Dyskinesia type (high dopa chorea [HDC], low dopa chorea [LDC], high dopa dystonia [HDD], and low dopa dystonia [LDD]) predicted response to treatment and whether or not levodopa dose reduction would benefit dyskinesias without producing unacceptable "offs." High dopa chorea improved best but at the expense of increased "off" time, followed by LDD, HDD, and LDC. Levodopa reduction was an acceptable strategy in ameliorating HDC and LDD only. Adjunctive therapy benefited all dyskinesia types, although the majority of patients (12/17) helped by selegiline had LDD or LDC. Generally, low doses of dopamine agonists were helpful (bromocriptine < 20 mg/day; pergolide < 2 mg/day). When adding adjunctive therapy (except for selegiline or controlled-release carbidopa/levodopa), concomitant reduction in daily dose of levodopa was not an effective strategy to decrease dyskinesias. Serial trials of multiple drug regimens are useful in these patients.
 ...
PMID:An analysis of treatment options and outcome in patients with Parkinson's disease and severe dyskinesias. 814 65