Dose-dependent subacute cardiovascular effects of modafinil in rats.

Modafinil is used for the treatment of various sleep disorders; however, its usage among healthy individuals is also increasing. There are a limited number of cardiovascular side effects, including ischemic T-wave changes, dyspnea, hypertension, and tachycardia in the literature. Our research aimed to investigate the dose-dependent subacute cardiovascular effects of modafinil in rats. Thirty-two rats were randomly and equally assigned to a control group (vehicle-treated for 14 days), a subacute low-dose group (SALD, 10 mg/kg for 14 days), a subacute moderate-dose group (SAMD, 100 mg/kg for 14 days), and a subacute high-dose group (SHD, 600 mg/kg for 14 days). The cardiovascular effects of modafinil were evaluated using hemodynamic, biochemical, electrocardiographic, electrophysiologic, and histopathologic parameters. In terms of hemodynamic parameters, heart rate, and systolic/diastolic/mean blood pressure levels, electrophysiological parameters did not reach statistical significance among the groups (p > 0.05). The incidence of T-wave negativity in SAMD and SAHD groups was 25 and 37.5%, respectively. Moreover, one rat per group was affected by an atrioventricular blockage. Malondialdehyde, superoxide dismutase, catalase, and reduced glutathione levels in the heart and vascular tissues, serum troponin-I, and creatine kinase levels were similar between the modafinil-administered groups and the control group (p > 0.05); this indicates that modafinil activated neither oxidative stress nor antioxidant pathway. Also, there was no difference in histopathological parameters between groups (p > 0.05). Supratherapeutic doses of modafinil may have the potential to cause ischemic cardiac damage and atrioventricular blockage, despite inconsistency with literature findings; however, this does not pertain to hemodynamic changes.

Memory improvement by modafinil at cost of metabolic hazards? A study to decipher the benefits and risks of modafinil in rats.

BACKGROUND: Modafinil is approved for narcolepsy and achieved high success in off-label indications in memory-related disorders. However, chronic indiscriminate use of modafinil imposes several health hazards like hyperglycaemia, obesity and metabolic syndrome, owing to impairment of sleep-wake cycle, circadian-rhythm, and neurotransmission. The present protocol elucidates the effects of modafinil per se and diabetic complications apropos. METHODS: Modafinil (100 and 200 mg/kg) was administered in rats from day 5-26. To induce type-2 diabetes, streptozotocin (STZ) was given on day 1, and blood glucose assessed on day 5. CPP (combination propranolol and phentolamine) was administered to antagonize sympathetic activity. After evaluation of cognitive functions, serum lipid profile, and biomarkers of oxidative stress and acetylcholinesterase (AChE) activity were assessed. RESULTS: Subacute dosing of modafinil significantly elevated blood glucose levels, albeit considerably less than diabetic group, and attenuated brain oxidative stress and AChE activity. Modafinil caused significant dyslipidaemia, increased body weight, whereas modestly altered abdominal circumference (AC) and thoracic circumference (TC) in rats. Significant hyperglycaemia, derangement of serum lipid-profile, brain lipid peroxidation, cholinergic hypofunction, and decrease in body weight and ACTC was noted in diabetic rats. Modafinil (100 mg/kg) significantly potentiated the hyperglycaemia and dyslipidaemia, however, attenuated oxidative stress and AChE activity in diabetic rats. Modafinil increased short-term (working) memory but not long-term spatial memory in normal and diabetic rats. CPP infusion attenuated these effects of modafinil. CONCLUSION: Subacute dosing of modafinil differentially modulates long-term and short-term memory subtypes, and also predisposes towards metabolic derangements.

The mutagenic effect of psychostimulant modafinil in Wistar rats in vivo.

The demands imposed by today's world require a fast and efficient society, then, significant section of the population looks for support from psychotropic medicine. Modafinil is a psychostimulant that promotes wakefulness, it being recommended for treatment of narcolepsy, obstructive sleep apnea, and shift-work sleep disorder, besides being a cognitive function potentiator. However, chemical components of drugs can alter genetic material. Thus, the present study evaluated the cytotoxic and clastogenic/mutagenic potential of 0.25, 0.50, and 0.75 mg of Modafinil/mL of corn oil/100g body weight in acute treatments and subacute treatments, 15 days, to Rattus norvegicus, treated via gavage in a single daily dose. The drug was not cytotoxic at any of the evaluated doses in either of the treatments. However, the medicine showed clastogenic/mutagenic activity in the acute treatment group at the standard dose and at double dose. Data from the present study indicates that there should be greater caution as to the use of this psychostimulant by human beings.

Nootropic drugs: Methylphenidate, modafinil and piracetam - Population use trends, occurrence in the environment, ecotoxicity and removal methods - A review.

Pharmaceuticals which originally were designed to treat people with neurological and psychiatric conditions, e.g. Alzheimer's disease or attention deficit hyperactivity disorder (ADHD), are nowadays often misused by students as a 'brain doping' substances. These substances are known as nootropic drugs, smart drugs or cognitive enhancers, as they increase memory, attention and concentration of healthy individuals. Since they are easily available illicitly, their consumption is observed to be growing. Currently, these pharmaceuticals started gaining researchers' attention, especially since they have been recently detected in wastewater, surface water and even drinking water. This review summarises the current state of knowledge on nootropic drugs in terms of their population use trends and ethics, occurrence in the environment and detection techniques, toxicity and removal methods, in example of methylphenidate, modafinil and piracetam - three most popular nootropics. It points out that the main sources of knowledge on cognitive enhancers illicit use are often inconsistent questionnaires, which are not supported by wastewater analysis to become more veracious. Simultaneously, the studies concerning toxicity and removal methods of nootropic drugs are still limited and in many cases environmentally irrelevant. Although the prescription rules has been subjected to more strict control in developed countries, regulatory frameworks with regard to their ecosystem occurrence are still lacking and should be introduced. Moreover, the use of environmentally relevant concentrations in toxicity studies should be a standard, leading to proper ecotoxicity risk assessment. Based on this review, it is recommended to routinely monitor nootropics and their metabolites in waste- and surface waters.