Modafinil is a psychostimulant medicine used to treat daytime sleepiness in persons with narcolepsy, obstructive sleep apnea, shift work sleep disorder, and other sleep-related illnesses. Modafinil is also used to treat shift work sleep disorder. It is touted as more potent than coffee while freeing the addiction danger associated with amphetamines. Since its approval for the treatment of narcolepsy, the use of modafinil has skyrocketed. It is now widely used to treat depression, attention deficit hyperactivity disorder (ADHD), tiredness, and sleepiness brought on by other drugs.
In addition, healthy people are abusing the drug modafinil for purposes other than medical in the expectation that it will improve their cognitive performance. Although modafinil seems to have a limited potential for abuse, excessive medication use in people who are not regular drug users can lead to euphoria or psychosis.
Because other stimulants, including amphetamine, cocaine, and the alkaloids found in ephedra, are known to elevate blood pressure and increase the risk of heart attacks. The effect that modafinil has on the cardiovascular system with lesser side effects has garnered a lot of attention. Few people who take Modafinil have reported experiencing increased heart rate and blood pressure.
Ongoing studies are looking into whether or not the autonomic nervous system is also involved in the cognitive boosting benefits, abuse potential, and anorexigenic effects of the substance in question. On the other hand, research is being conducted with human participants to learn how modafinil influences the activity of the muscular sympathetic nerve and the levels of catecholamines.
The expanding use of modafinil in clinical medicine and as a cognitive enhancer, as well as the mystery surrounding the mechanisms that underlie its pharmacological effects, highlight the need for a deeper understanding of the drug’s mechanisms of action. This need has been brought to light by the fact that there currently needs to be more understanding. Because the use of modafinil is quickly growing, it is of the utmost importance to determine how the drug influences the autonomic cardiovascular regulation of healthy people.
Sympathomedullary Pathway (SAM Pathway) :
The SAM Pathway is the route the brain takes to direct activity in the sympathetic branch of the autonomic nervous system (ANS), which becomes active in response to transiently elevated stress levels. The hypothalamus stimulates the sympathetic branch of the autonomic nervous system (ANS), which in turn causes the adrenal medulla to secrete adrenaline and noradrenaline.
When active, the sympathetic nervous system has a direct connection to the heart; this connection is responsible for the increase in blood pressure and the acceleration in heart rate that occurs when it is active. The discharge of noradrenaline and adrenaline both intensifies and maintains the effects of the stress response. The result is that the muscles receive oxygen more quickly, which enables them to engage in more strenuous physical activity. All these train a person for the proverbial “fight or flight” scenario.
These responses are brought on by hormones associated with stress, such as cortisol and catecholamines (adrenaline and norepinephrine). The presence of an excessive amount of cortisol in the blood can have a variety of adverse effects. It may have psychological effects such as anxiety or depression.
The stress hormone cortisol causes the stores of glucose in our bodies to be released, which has various physiological effects, including increased appetite, higher blood pressure, and an increased risk of developing type 2 diabetes.
Cortisol encourages the production of more stomach acid so our cells can get the nutrients they need to perform effectively. It also helps our systems become more efficient at absorbing nutrients. Consuming an excessive amount of this substance may cause problems with the gastrointestinal tract, such as nausea, indigestion, stomach pain, diarrhea, or vomiting.
Effects of Modafinil on SAM Pathway:
When the sympathetic nervous system is activated, it results in the release of stress hormones, including cortisol and adrenaline, which is known as sympathomedullary activation. It is commonly believed that activation of the sympathetic nervous system in reaction to stress is a harmful response. It’s possible that modafinil could help reduce the detrimental effects of activity in the sympathetic nervous system.
The body’s serotonin and dopamine levels may increase, which may help to calm the body and reduce the production of hormones associated with stress. Resting HR and BP will remain elevated. Consequently, there is a slight increase in the autonomic function and reflex sensitivity tests. The levels of L-Dopa, adrenaline, and NE in the urine were all shown to be significantly elevated. The stories of creatinine are unchanged by modafinil’s presence.
Recent research has shown that taking modafinil can lead to significant increases in both blood pressure and heart rate, as well as a protracted stimulation of the adrenomedullary system. This is the most important discovery that has come out of this research.
The fact that there was no difference in the amount of sodium or potassium excreted through urine is conclusive evidence that the increase in blood pressure was not the result of sodium retention due to the expansion of the extracellular fluid. According to the electrolytes in urine, the pressor effect cannot be explained by any mechanism that involves a rise in mineralocorticoids.
The changes in epinephrine were, on average, more significant than the changes in NE. The levels of epinephrine were found to be significantly elevated in the arterial pathway. The ratio of epithelial to neuronal excitability (Epi/NE) following modafinil is higher when compared to other sympathetic stimuli, such as salt restriction and an upright position. This increased Epi could stimulate the release of neurotransmitter NE from neuron terminals in a roundabout way.
The rise in dopa levels and its metabolite DOPAC indicates an increase in tyrosine hydroxylase activity. It may be the result of sympathetic stimulation or an improvement in the enzyme’s activity, as demonstrated by the rise in dopa levels.
It is doubtful that the norepinephrine transporter or monoamine oxidase is the biochemical pathway through which modafinil exerts its effects (NET). DHPG is driven higher because of increased NE synthesis and leakage, which leads to a little NET blockage. However, this is offset by increased central sympathetic outflow. Thus the overall effect is neutralized.
Increases in NE, epinephrine, L-dopa, DOPAC, heart rate, and blood pressure should be expected to be accompanied by a rise in microneurography bursts. On the other hand, there is an increasing incidence of sympathetic activation in various organs.
To conclude, modafinil induces a robust central adrenergic response, as shown by elevated levels of catecholamines (plasma NE, dopa, DOPAC, urine NE, and Epi), HR, and BP. This reaction is indicative of the drug’s stimulant properties. The adrenergic stimulation that modafinil causes could lead to an increase in the number of people who have high blood pressure. Because of this, modafinil should be used with caution in individuals with cardiovascular disease or who are participating in strenuous physical activity.
