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

A single dose of haloperidol and reduced haloperidol has been found to exacerbate the dystonic response produced by U50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl) -cyclohexyl]-benzeacetamide methane sulphonate) in guinea-pigs [8]. The present study sought to correlate the behavioural effect of haloperidol and reduced haloperidol with their effect on inhibition of sigma binding sites in guinea-pig brain using receptor binding and semi-quantitative autoradiography. In the first experiments, groups of guinea-pigs were injected with saline (control, n = 12), haloperidol (0.1 and 1 mg/kg i.p., n = 5) or reduced haloperidol (0.1 and 1 mg/kg i.p., n = 5) 1, 3 and 10 days before, followed by U50,488H (10 mg/kg s.c.) and the effect on the dystonic response rated using a behavioural rating scale [8]. In the second experiments, animals (n = 5) were injected with saline, haloperidol and reduced haloperidol as above and killed 1, 3 and 10 days later, their brains removed, dissected and tissue sections processed for sigma binding site autoradiography using [3H]3-(3-hydroxyphenyl)-N-(n-propyl)piperidine ([3H]-3-PPP). Triplicate tissue sections were wiped using GF/C filters and radioactivity counted. Injection of haloperidol and reduced haloperidol 1, 3 and 10 days earlier exacerbated the dystonic response by decreasing the latency to maximal dystonia and increasing the duration of the response at each dose tested compared with saline-treated animals. These effects of haloperidol and reduced haloperidol on latency and duration were time-related since the effect at 1 > 3 > 10 days. In addition, [3H]-3-PPP binding was inhibited by haloperidol and reduced haloperidol in a dose-and time-related manner. For example, % inhibition of [3H]-3-PPP binding for haloperidol (1 mg/kg) > haloperidol (0.1 mg/kg) and % inhibition of binding (mean +/- SEM) produced by haloperidol (0.1 mg/kg) at 1 (96.1 +/- 2.4) > 3 (74.8 +/- 4.8) > 10 days (36.2 +/- 1.6). Similar results were obtained for haloperidol (1 mg/kg) and reduced haloperidol (0.1 and 1 mg/kg). [3H]-3-PPP autoradiography confirmed these binding data. The results indicate that the exacerbation by sigma ligands of the dystonia produced by U50,488H was associated with the degree of inhibition of [3H]-3-PPP binding.
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PMID:Haloperidol and reduced haloperidol-induced exacerbation of the dystonia produced by the kappa opioid U50,488H in guinea-pigs is associated with inhibition of sigma binding sites: behavioural and autoradiographical studies. 758 12

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.
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PMID:Effects of several partial dopamine D2 receptor agonists in Cebus apella monkeys previously treated with haloperidol. 810 65

To clarify clinical roles of sigma receptor binding affinity of neuroleptics, neck dystonia induced by microinjection of sigma receptor ligands and neuroleptics into rat red nucleus was investigated. DTG and (+)-3-PPP, putative sigma receptor agonists, induced neck dystonia in dose-dependent and reversible manner. Haloperidol and perphenazine induced dystonia in the same way as sigma receptor agonists, whereas zotepine and (-)-sulpiride did not. The rank order of potency in induction of dystonia and sigma receptor affinity of these compounds showed positive correlation. Although BMY-14802 has a high affinity for sigma receptors, it never produced dystonia by itself. On the other hand, combined injection of BMY-14802 with DTG attenuated DTG-induced dystonia. Therefore, it is suggested that typical neuroleptics such as haloperidol act agonistic and atypical neuroleptics such as BMY-14802 act antagonistic at rubral sigma receptors in the induction of neck dystonia.
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PMID:BMY-14802 reversed the sigma receptor agonist-induced neck dystonia in rats. 901 2