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)

Haloperidol exhibits a high affinity for a subclass of sigma- "opiate" binding sites which have a unique anatomic distribution and a unique drug selectivity pattern. These binding sites differ from phencyclidine-sensitive sigma-receptors and are found in many brain areas involved in the control of movement. 1,3-Di-o-tolylguanidine (DTG), a highly selective ligand for the haloperidol-sensitive sigma-receptor, produced marked dystonia in rats after microinjection into the red nucleus, a motor area rich in this receptor. Haloperidol and another sigma-ligand [(+)-SKF 10,047] produced similar effects. On the other hand, clozapine, an antipsychotic drug which fails to bind to sigma-receptors and fails to induce movement disorders in humans, failed to induce these dystonic reactions in rats. Phencyclidine was also without effect, as were injections of the active compounds in sites distant to the red nucleus. Microinjections of DTG in the substantia nigra produced vigorous contralateral circling behavior at extremely low doses. These findings suggest that sigma-binding sites represent biologically functional receptors that are active in the neural control of movement. Since haloperidol (and many other antipsychotic drugs) exhibit an affinity for sigma-receptors which is at least equal to its affinity for dopamine receptors, these data raise the further possibility that sigma-receptors are involved in the motor side effects of antipsychotic drugs.
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PMID:Evidence for a role of haloperidol-sensitive sigma-'opiate' receptors in the motor effects of antipsychotic drugs. 289 93

1,3,-Di-o-tolylguanidine (DTG), a sigma agonist, produces hypothermia in rats, but the inability of purported sigma antagonists to block the hypothermia suggests that sites other than sigma may mediate the effect. Recently, N-[2-(3,4-dichlorophenyl) ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD 1047) has been identified as a functional sigma antagonist in vivo because of its high selectivity for sigma sites and its ability to block DTG-induced dystonia and cocaine-evoked behaviors. Therefore, the present study investigated the effect of BD 1047 on DTG-evoked hypothermia. DTG (1, 10, 20 and 30 mg/kg sc) induced dose-dependent hypothermia. The onset of DTG-induced hypothermia was rapid, with a reduction in body temperature observed 15 min postinjection. To determine whether sigma sites mediated DTG-induced hypothermia, BD 1047 was injected 30 min prior to DTG. BD 1047 (1, 5, 7.5 and 10 mg/kg sc) attenuated the hypothermia in a dose-dependent fashion, thus revealing a sigma site mechanism. The injection of BD 1047 alone did not alter body temperature, suggesting that endogenous sigma systems do not play a tonic role in thermoregulation. The present experiments demonstrate for the first time that a selective sigma antagonist attenuates sigma agonist-induced hypothermia. Moreover, these data provide further evidence that BD 1047 is an effective antagonist for characterizing sigma-mediated effects in vivo.
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PMID:Sigma sites mediate DTG-evoked hypothermia in rats. 1221 22