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Dopamine does not cross the blood–brain barrier, so its synthesis and functions in peripheral areas are to a large degree independent of its synthesis and functions in the brain. [26] A substantial amount of dopamine circulates in the bloodstream, but its functions there are not entirely clear. [27]
The CTZ is located within the area postrema, which is on the floor of the fourth ventricle and is outside of the blood–brain barrier. [1] It is also part of the vomiting center itself. [ 2 ] The neurotransmitters implicated in the control of nausea and vomiting include acetylcholine , dopamine , histamine (H1 receptor), substance P (NK-1 ...
The blood–brain barrier (BBB) is a highly selective semipermeable border of endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the central nervous system, thus protecting the brain from harmful or unwanted substances in the blood. [1]
The area postrema is very sensitive to changes in blood toxicity and senses the presence of poisonous or dangerous substances in the blood. As a defense mechanism, the area postrema induces vomiting to prevent further intoxication. The high density of dopamine receptors in the area postrema makes it very sensitive to the dopamine-enhancing drugs.
The cells of the neurovascular unit also make up the blood–brain barrier (BBB), which plays an important role in maintaining the microenvironment of the brain. [11] In addition to regulating the exit and entrance of blood, the blood–brain barrier also filters toxins that may cause inflammation, injury, and disease. [12]
The blood–brain barrier is formed by special tight junctions between endothelial cells lining brain blood vessels. Blood vessels of all tissues contain this monolayer of endothelial cells, however only brain endothelial cells have tight junctions preventing passive diffusion of most substances into the brain tissue. [1]
Levodopa is also too polar to cross the blood brain barrier but it is an amino acid and has a specialized transporter called L-type amino acid transporter or LAT-1 that helps it diffuse through the barrier. [32]
Peripherally selective DDCIs incapable of crossing the protective blood–brain barrier (BBB) are used in augmentation of L-DOPA (levodopa) in the treatment of Parkinson's disease (PD) to block the conversion of L-DOPA into dopamine outside the brain, for the purpose of reducing adverse side effects. [3]