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Migraine
Published in M.D. Francesco Amenta, Peripheral Dopamine Pathophysiology, 2019
Marcello Fanciullacci, Massimo Alessandri, Bruno M. Fusco
Studies in normal volunteers with lisuride (50 μg i.v.)13 and apomorphine (10 to 30 μg/ kg i.m.)14 indicate that DA agonists provoke a typical spectrum of side-effects which includes nausea, emesis, constipation, orthostatic hypotension, drowsiness and sedation, and sometimes, long-lasting episodes of headache. With the exception of this last symptom, administration of domperidone prevents or treats these disturbances quite effectively, thus indicating that they depend on DA receptors located outside the BBB.13
l -Theanine ameliorates motor deficit, mitochondrial dysfunction, and neurodegeneration against chronic tramadol induced rats model of Parkinson’s disease
Published in Drug and Chemical Toxicology, 2022
Khadga Raj, G. D. Gupta, Shamsher Singh
Additionally, long-term toxin exposure and excessive use of opioid drugs like tramadol enhance oxidative stress, alter neurotransmitters level, and damage to dopaminergic neurons. Reduced neutralization and overproduction of ROS can lead to mitochondrial damage, including mutations in mitochondrial DNA, affect to the mitochondrial respiratory chain, permeability, and disruption to Ca2+ homeostasis. Therefore, mitochondrial damage plays an important role in the pathogenesis of neurodegenerative diseases including PD (Guo et al.2013). The available treatments of PD only increase the dopamine level in the striatum to restore the associated motor deficits. These includes dopamine precursor (levodopa), agonists of dopamine (ropinirole, pramipexole, lisuride, and rotigotine), MAO-B inhibitors (rasagiline and selegiline). However, these approaches do not provide long-term neuroprotection (Velázquez-Paniagua et al.2016). Similarly, long-term use of dopamine precursor is reported to initiate abnormal movements such as dyskinesia, known as l-DOPA induced dyskinesia (LID) and reduces motor ability in PD (Cenci 2014). Presently, available drugs provide symptomatic benefits without reversion or slowing of disease pathogenesis. Hence, there is a need to find out potential drug molecules or target sites that can overcome PD (Oertel 2017).
New approaches to discovering drugs that treat dystonia
Published in Expert Opinion on Drug Discovery, 2019
Sarah Pirio Richardson, H. A. Jinnah
Interestingly, despite both the link between dystonia and dopamine, dopamine agonism is not commonly used as a treatment for dystonia, except for specific cases like dopa-responsive dystonia. There was an attempt in the past to test dopamine receptor agonists, starting in the 1940s and largely ending by the mid-1980s due to lack of apparent efficacy as well as side effects that were deemed intolerable [38]. Agents studied included both indirect-acting agents (amphetamine) as well as direct agonists (apomorphine, bromocriptine, and lisuride). Overall there was some signal of effect ranging from 63% of the patients tested with apomorphine (D1/D2) to lesser efficacy for the D2 receptor agonists, bromocriptine and lisuride [38]. However, there were challenges in study design such as inclusion of multiple subtypes of dystonia, which can make detection of efficacy difficult due to etiological heterogeneity, wide-ranging symptomatology, and equally wide-ranging outcome measures. Given this background, it may be premature to conclude that dopamine receptor agonists do not play a role in the treatment of dystonia, more widely. Although moving forward, it appears that D1/D2 agonism may have a greater signal of effect and may be the first target for novel therapeutic development in this area, and systematic clinical trials in a homogeneous population are needed [38].
Dopamine-induced functional activation of Gαq mediated by dopamine D1-like receptor in rat cerebral cortical membranes
Published in Journal of Receptors and Signal Transduction, 2019
Yuji Odagaki, Masakazu Kinoshita, Toshio Ota
Among the nonselective dopamine receptor agonists investigated, R(+)-lisuride was the most potent stimulator with a mean log(max/EC50) of 7.79 (Figure 4). Stimulatory effects were also elicited by pergolide, (+)-bromocriptine, and R(-)-apomorphine, with submicromolar EC50 values. Remarkably, the maximum stimulatory effects of pergolide (%Emax = 239%) exceeded the %Emax values of dopamine (99.1%). Although the other two compounds R(-)-propylnorapomorphine (Figure 4) and rotigotine appeared to stimulate the binding at higher concentrations investigated (i.e. 100 μM), their EC50 and %Emax values were unable to determine due to lack of reasonable pharmacologically relevant sigmoid curves.