Molecular targets of caffeine in the central nervous system

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madman

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Abstract

Caffeine is an alkaloid obtained from plants and is one of the most consumptive drug in the form of chocolate, coffee and beverages. The potential impact of caffeine within CNS can be easily understood by mechanism of action-antagonism of adenosine receptor, calcium influx, inhibits phosphodiesterases. Adenosine a neuromodulator for adenosine receptors, which are abundantly expressed within the central nervous system. Caffeine antagonized the adenosine receptor, hence stimulate expression of dopamine. It plays pivotal role in many metabolic pathways within the brain and nervous system, it reduced the amyloid-β-peptide (Aβ) accumulation, down regulation of tau protein phosphorylation, stimulate cholinergic neurons and inhibits the acetylcholinestrase (AChE). It also possess antioxidant and antiapoptotic activity. Caffeine act as nutraceutical product, improves mental health. It contains antioxidants, vitamins, minerals and dietary supplements, by reducing the risk factor of several neuro degenerations including Alzheimer’s disease, migraine, gallstone, cancer, Huntington’s disease and sclerosis. This act as a stimulant and have capability to increase the effectiveness of certain painkiller. Beside positive affects, over-consumption of caffeine leads to negative impact:change in sleep pattern, hallucinations, high blood pressure, mineral loss and even heartburn. This chapter highlights pros and cons of caffeine consumption.




1. Introduction

Caffeine is an organic molecule found in plant constituents such as cocoa beans, chocolate and coffee and is added to variety of food in baked pastries, soft drinks and ice creams. It is also present in food supplements for weight loss and even in medicine and cosmetics as well. It has been observed that this can be taken orally as it is rapidly absorbed by the human body. Historically Caffeine being used as medical nutrient because of easily absorption. In the 10th century, Avicenna, a Persian physician, introduced coffee as a medicinal remedy in his work “The Canon of Medicine”. Initially, coffee was utilized for cleansing the skin, reducing underlying humidities, and enhancing body odor. By the 15th century, coffee gained popularity among Muslim dervishes as an energy booster, leading to its widespread diffusion and the establishment of numerous coffee houses in Arabia. With the expansion of sea shipping in the late 17th and 18th centuries, coffee became increasingly prevalent in Europe.

It is the main psychoactive constituent of coffee and was isolated from coffee beans in 1820. It has been reported that several non-prescriptive drugs and analgesics contain drugs. It act as stimulant for the central nervous system by reducing sleep and improving mental alertness. One of the most widely enjoyed and beneficial drinks globally is coffee (Frary et al., 2005). Caffeine is one of the consumptive drug can occur in various forms such as coffee, soda and chocolate and
act as stimulant for the central nervous system (CNS). It has great potential in energy metabolism and also activates the noradrenaline neurons. The main effects of caffeine involve various type of stimulant act upon the brain. Coffee being the most healthiest beverages and natural metabolites which provide beneficial effects on health including neuroprotective and cardioprotective whereas heavy consumption leads anxiety, headache and high blood pressure. Coffee improves the memory through cerebral action. It has been reported that parasympathetic and sympathetic acts upon the autonomic system. The blood–brain barrier (BBB) & the blood–cerebrospinal fluid barrier (BCSFB) are the major site for stimulants and are necessary for chemical kinetics for drugs. Within the CNS ,adenosine receptor are responsible for regulation of neurotransmitter and also control the sleep pattern, cognitive learning and memory. Caffeine binds to that specific receptor which leads to blockage of receptors in terms of influx of neurotransmitters including dopamine, norepinephrine, glutamate, and gamma-aminobutyric acid (GABA) leads to mood alterations.




2. Origin


3. Caffeine: Central nervous system stimulant


4. Caffeine and brain structure


5. Biochemistry and metabolic pathway of caffeine

5.1 Adenosine receptor
5.2 Calcium mobilization
5.3 Caffeine and cyclic adenosine monophosphate (cAMP)
5.4 Mechanism of action of caffeine



6. Pros of caffeine consumption on central nervous system
6.1 Adenosine and sleep pattern
6.2 Pain modulation



7. The influence of caffeine on sleep patterns and migraine occurrence


8. Impact of maternal caffeine consumption on fetal brain development


9. Caffeine and neurodegenerative diseases

9.1 Parkinson’s disease (PD)
9.2 Huntington’s disease (HD)
9.3 Alzheimer’s disease (AD)
9.4 Machado-Joseph disease (MJD)
9.5 Amyotrophic lateral sclerosis (ALS)
9.6 Cons of caffeine consumption





10. Conclusion

Adenosine, often referred to as the “sleep regulator” is produced in response to neuronal function and interacts with A1 and A2A receptors in the brain, including the basal ganglia and cortex. Its actions involve inducing global cortical disfacilitation and stimulating sleep-active neurons in the hypothalamus, thereby modulating brain functions associated with the regulation of sleep pattern, such as mental and physical attention. Accumulated evidence from pharmacological and genetic studies conducted in individuals suggests that variations in adenosinergic activity primarily impact vigilant attention, irrespective of sleep status. Caffeine, acting as a non-selective antagonist of A1 and A2A receptors, mitigates the physiological and behavioral aspects related to neuronal activity, effects of sleep deprivation. However, it does not serve as a complete substitute for sleep, and standard doses fail to enhance cognitive learning and memory are compromised by severe sleep loss. It was noted that the hazards associated with caffeine are linked to its widespread availability, which often leads to unintentional excessive consumption. This is due to the difficulty in accurately gauging daily intake and predicting specific effects. It was also observed that, similar to other psychoactive substances, caffeine has the capability to induce dependence. Unlike alcohol and tobacco, though, there are fewer controls or restrictions on the sale of high-concentration caffeine products such as drinks or tablets. Recently, researches provide a way to determine the effect of caffeine on mood swing and majority of studies to help enable the memory and cognitive learning tasks. It has been reported that caffeine plays crucial role in short-term as well as long-term memory.
 

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Fig. 1 Name of Bioactive compound found in Coffee.
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