Tobacco use is the single most preventable cause of death, disability and disease in the world and is projected to be the leading cause of death and disability across all developed and developing countries by 2020. Nicotine, the primary active ingredient of cigarettes that contributes to physical dependence, acts on nicotine receptors in the central nervous system and leads to the release of neurotransmitters (such as dopamine). Like other drugs of abuse, nicotine is thought to produce reinforcing effect by activating the mesocorticolimbic dopamine system. A wide variety of cessation treatments of nicotine dependence is commercially available, yet only 2 general approaches have received empirical validation: behavioral intervention (including 5 As brief intervention) and pharmacotherapy. The evidences show that 5 As brief intervention is one of the most cost-effective treatments in clinical work for busy physicians. Three types of medications have been available in market for smoking cessation treatment: nicotine replacement treatment (NRT, i.e., transdermal patch, gum, inhaler, nasal spray, and lozenge), sustained release bupropion and varenicline. Varenicline, a novel alpha4beta2 nicotinic receptor partial agonist, is effective for tobacco dependence. Phase III trials suggest that it is more effective than NRT and bupropion SR. The safety profile of varenicline is excellent, with the most commonly occurring adverse events, nausea, typically mild and well tolerated. However, new safety warnings are added to the varenicline label because of post-marketing report including agitation, depression and suicidality. A causal connection between varenicline use and these symptoms has not been established.
Benzazepines ; adverse effects ; therapeutic use ; Bupropion ; therapeutic use ; Dopamine Uptake Inhibitors ; therapeutic use ; Humans ; Nicotinic Agonists ; adverse effects ; therapeutic use ; Quinoxalines ; adverse effects ; therapeutic use ; Smoking Cessation ; methods ; psychology ; Tobacco Use Disorder ; therapy ; Varenicline

This report describes the efficacy of combined use of aripiprazole in the treatment of a patient with clozapine induced enuresis. Aripiprazole acts as a potential dopamine partial agonist and the dopamine blockade in the basal ganglia might be one of the causes of urinary incontinence and enuresis. We speculate that aripiprazole functioned as a D2 agonist in hypodopaminergic state of basal ganglia caused by clozapine and maintained dopamine level that would improve enuresis ultimately.
Adult ; Antipsychotic Agents/*adverse effects ; Clozapine/*adverse effects ; Dopamine/metabolism ; Dopamine Agonists/*therapeutic use ; Drug Therapy, Combination ; Enuresis/chemically induced/*drug therapy ; Humans ; Male ; Middle Aged ; Piperazines/*therapeutic use ; Quinolones/*therapeutic use ; Schizophrenia, Paranoid/drug therapy

Erectile dysfunction is a common disease of andrology, for which current guidelines recommend oral agents as the first-line therapy. The dopamine agonist apomorphine acts on the central control of penile erection to allow a sublingual preparation to produce a prompt response. It is not contraindicated in patients on nitrate medication for coronary artery disease. The present review describes the pharmacodynamics, action mechanism, efficacy and adverse effects of apomorphine.
Apomorphine ; adverse effects ; pharmacokinetics ; therapeutic use ; Dopamine Agonists ; adverse effects ; pharmacokinetics ; therapeutic use ; Erectile Dysfunction ; drug therapy ; physiopathology ; Humans ; Male ; Penile Erection ; drug effects

BACKGROUNDNurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson's disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.

METHODSThe mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.

RESULTSThe relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).

CONCLUSIONSDA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.

Adult ; Aged ; Aged, 80 and over ; Dopamine Agonists ; therapeutic use ; Female ; Humans ; Leukocytes, Mononuclear ; drug effects ; metabolism ; Male ; Middle Aged ; Nuclear Receptor Subfamily 4, Group A, Member 2 ; genetics ; Parkinson Disease ; drug therapy ; genetics ; RNA, Messenger ; genetics ; Young Adult