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)

The genetically dystonic (dt) rat is an animal model of dystonia that displays sustained abnormal movements that include: torticollis, clasping of the hindlimbs, rigidity of the limbs, and contortions of the trunk. Since serotonin (5-HT) has been shown to be involved in some animal models of movement disorders, the functional responsiveness of the 5-HT system in dt rats and phenotypical normal littermates was examined by administering 5-HT agonists selective for different receptor subtypes and observing behavioral responses associated with the activation of specific 5-HT receptor subtypes. The dt rats were 6-fold more sensitive to the ability of the 5-HT1A agonist 8-OH-2-(di-n-propylamino)tetralin (8-OH-DPAT) to produce the 5-HT behavioral syndrome. The dt rats demonstrated a diminished head-shaking response following administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB). However, the dt rats also displayed significantly fewer head shakes following mechanical stimulation of the aural pinnae. The inability of the dt rats to demonstrate head-shaking behavior following stimulation of 5-HT2 receptors is probably due to the dt rat's difficulty in producing the motor responses involved in this behavioral response and do not reflect alterations in 5-HT2 receptor sensitivity. These results suggest that the 5-HT system, particularly 5-HT1A receptors, may have an integral role in the abnormal movements displayed by the genetically dystonic rat and movement disorders in general.
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PMID:Altered behavioral responses mediated by serotonin receptors in the genetically dystonic (dt) rat. 201 8

The genetically dystonic (dtsz) hamster is an autosomal recessive mutant that shares several features with paroxysmal dystonia, i.e., a subcategory of inherited idiopathic dystonia in humans. Because the serotonin (5-HT) system has been suggested to be involved in dystonia, we examined the functional responsiveness of the 5-HT system in dystonic hamsters by administering various 5-HT agonists and antagonists selective for different receptor subtypes and observing the effects on dystonic attacks as well as the behavioural responses associated with drug administration. Paradoxically, marked prodystonic effects (i.e., increased severity and/or decreased latency of dystonic attacks) were seen with both the selective 5-HT1A receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) and the selective and "silent" 5-HT1A receptor antagonist, N-tert-butyl-3[4-(2-methoxyphenyl)piperazin-1-yl]-2- phenylpropionamide [(+)-WAY-100135], whereas other 5-HT1A receptor antagonists, i.e., methyl 4[4-(4-[1,1,3-trioxo-2H-1,2-benzoiosothiazol-2-yl]butyl)-1- piperazinyl]1-H-indole-2-carboxylate (SDZ 216-525) and N1-bromoacetyl-N8-3'-(4-indolyloxy)-2'-hydroxypropyl-(Z)-1,8- diamino-p-methane (pindobind-5-HT1A) did not alter dystonia to any comparable extent. Because among these 5-HT1A receptor antagonists, (+)-WAY-100135 is the only drug known to be not only silent at postsynaptic but also presynaptic (somatodendritic) 5-HT1A receptors, the marked prodystonic effect of this drug could relate to increased 5-HT release as a result of the blockade of somatodendritic 5-HT1A receptors. The only 5-HT1A receptor antagonist that exerted antidystonic effects in hamsters was pindolol, which, however, could be related to its beta-adrenoceptor blocking action. The 5-HT1A receptor partial agonist ipsapirone exerted moderate prodystonic activity. Prodystonic activity was also determined for the mixed 5-HT1A/5-HT2 receptor agonist 5-methoxy-N,N-dimethyltryptamine, although this drug was less potent in this regard than 8-OH-DPAT. The 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) exerted prodystonic effects in mutant hamsters, which, however, were also seen after the administration of the 5-HT2 receptor antagonist ritanserin. Collectively, the results of this study demonstrate that dystonia in genetically dystonic hamsters can be affected by pharmacologic manipulation of 5-HT receptors. The data may also indicate that dystonia is not a potential clinical application for selective 5-HT1A or 5-HT2 receptor antagonists.
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PMID:Behavioural response to pharmacologic manipulation of serotonin receptors in the genetically dystonic hamster. 858 1

Objective: Selective serotonin reuptake inhibitors (SSRIs) have been the most widely used psychopharmacological agents prescribed for depression worldwide. Some adverse effects of SSRI drugs on central nervous system are insomnia and bruxism. These drugs also affect sleep. Quetiapine is used as adjunctive therapy to antidepressants for the treatment of major depressive disorder (MDD). It is a low- dose dibenzothiazepine with more potent 5-HT2 than D2 receptor-blocking properties that can be used to manage bruxism because of its antagonist effect on the 5-HT2 receptor. Cases: The cases were 5 patients who have recently been treated with SSRIs and presented with bruxism. Low- dose quetiapine (between 25 and 50 mg daily) was prescribed for the patients, and after a few days, they reported no bruxism and continued taking the medication. Conclusion: We found that quetiapine can improve bruxism and mandibular dystonia, which are side effects of SSRIs.
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PMID:Low-Dose Quetiapine in the Treatment of SSRI-Induced Bruxism and Mandibular Dystonia: Case Series. 3031 7