Experimental treatment of antipsychotic-induced movement disorders

Abstract

Antipsychotic drugs are extensively prescribed for the treatment of schizophrenia and other related psychiatric disorders. These drugs produced their action by blocking dopamine (DA) receptors, and these receptors are widely present throughout the brain. Therefore, extended antipsychotic use also leads to severe extrapyramidal side effects. The short-term effects include parkinsonism and the later appearing tardive dyskinesia. Currently available treatments for these disorders are mostly symptomatic and insufficient, and are often linked with a number of detrimental side effects. Antipsychotic-drug-induced tardive dyskinesia prompted researchers to explore novel drugs with fewer undesirable extrapyramidal side effects. Preclinical studies suggest a role of 5-hydroxytryptamine (serotonin)-1A and 2A/2C receptors in the modulation of dopaminergic neurotransmission and motivating a search for better therapeutic strategies for schizophrenia and related disorders. In addition, adjunctive treatment with antioxidants such as vitamin E, red rice bran oil, and curcumin in the early phases of illness may prevent additional oxidative injury, and thus improve and prevent further possible worsening of related neurological and behavioral deficits in schizophrenia. This review explains the role of serotonergic receptors and oxidative stress, with the aim of providing principles for prospect development of compounds to improve therapeutic effects of antischizophrenic drugs.

Buspirone-associated Movement Disorder: A Literature Review

“…BUS was withdrawn, and within one month the individual had a full recovery of the motor symptoms. Figure 4 shows a resume of the mechanisms to explain the BUS-use for neuropathic pain (dorsal horn) and dyskinesia (dorsal raphe) (Shireen, 2016;Haleem et al, 2018). We believe that some of the movement disorders can be explained by the same process as represented by the treatment of these two pathologies.…”

“…Some individuals had a previous diagnosis of DKN, and when BUS was used, they had a worsening of DKN (Bonifati et al, 1994). One of the hypotheses to explain the development of DKN involves the relationship of the serotonin, dopamine, and glutamate neurotransmitters in the striatum (Figure 5) (Floresco and Magyar, 2006;Shireen, 2016;Sokoloff and Le Foll, 2017;Atoji and Sarkar, 2019). Especially antipsychotics with dopamine D2 blockage can provoke an inflammatory process and release reactive oxygen species causing an abnormal adaptation of the striatal organization, and ultimately leading to…”

“…overactivation of the direct pathway (Lepping et al, 2011). With this background, the benefit of BUS for the management of DKN is due to the agonism of 5HT1A (coupled to the Gi protein and mediates inhibitory neurotransmission) that decrease the release and synthesis of serotonin; the serotonin concentration decrease causes a reduction of 5HT2C (coupled to the Gq protein and mediates excitatory neurotransmission) activity, which reduces the release of dopamine (Shireen, 2016). We believe that in some older individuals BUS may cause a selective block of D2 more than the agonism in 5HT2A can hold.…”

Predicting parkinsonism side-effects of antipsychotic polypharmacy prescribed in secondary mental healthcare

“…Our results reflect predictions based on minimal clinical information (antipsychotic names and doses) and we believe that adding further information such as age, gender and other medications prescribed in conjunction with the APP might further improve the predictive power of the model. For example, evidence indicates that benzodiazepines that increase GABA tone can also modulate EPS liability ( Susatia and Fernandez, 2009 ), similar to serotoninergic modulation with antidepressants ( Shireen, 2016 ). The QSP model has over 35 different CNS targets that encompass the pharmacology of most approved CNS active medications.…”

Tardif Diskinezi ve Tedavi Yaklaşımları

“…TD mekanizmasında birçok teori öne sürülmüştür. Dopamin blokajı dışında da farklı mekanizmalar üzerinde durulmuş, bu mekanizmaların doğrudan ya da dolaylı olarak nigrostrial yolu etkiledikleri düşünülmüştür (Shireen 2016). Nigrositriatal yolaktaki dopamin reseptör sisteminde aşırı duyarlılık, dopaminerjik ve kolinerjik sistemler arasındaki dengenin bozulması, striatonigral GABA'erjik nöronlarda işlev bozuklukları ve eksitotoksisite üzerinde durulmaktadır (Kulkarni ve Naidu 2003).…”