Dopamine and Hypertension
M.D. Francesco Amenta in Peripheral Dopamine Pathophysiology, 2019
The role of the third catecholaminergic neurotransmitter, dopamine (DA), on the cardiovascular system has been investigated. Several potential sources of DA could act on the vasculature: DA can be released from specific peripheral dopaminergic neurons or from sympathetic nerve endings; DA may reach the tissue via the blood under an intact form or as a conjugate which is then transformed into free amine. This chapter summarizes some physiological and pharmacological data implicating central and peripheral DA in the pathophysiology of arterial hypertension. Several types of peripheral dopaminergic receptors have been characterized: DA 2 prejunctional receptors on noradrenergic nerve terminals or ganglia, and DA 1 postjunctional dopaminergic receptors in renal, mesenteric, coronary, and cerebral vasculature and endocrine systems. Two main origins DA can be described in the body: first, renal dopaminergic nerves and second, the metabolic pathways from plasma l-dopa to DA.
Receptor-mediated transport
Neena Washington, Clive Washington, Clive Wilson in Physiological Pharmaceutics, 2001
The brain capillary endothelium possesses a number of receptors which allow the transport of specific materials. These include small molecule nutrient receptors, such as those for hexose, amino acids, amines, and a number of peptide and protein receptors, including those for insulin, transferrin and IGF-II26. It is possible to take advantage of these pathways for the delivery of mimetic drugs; for example, dopamine is poorly transported through the blood brain barrier, and its administration is of no direct therapeutic value, but the aminoacid analogue L-DOPA is transported through the phenylalanine receptor and can thus exert a useful pharmacological effect27.
Biogenic amines
William Nyhan, Georg Hoffmann, Bruce Barshop, Aida Al-Aqeel in Atlas of Inherited Metabolic Diseases 3E, 2012
AADC deficiency was first reported by Hyland and Clayton [1] and Hyland et al. [2] in twins who were very hypotonic, and had interspersed bouts of crying and paroxysmal movements of the arms and legs along with oculogyric crises. They developed abnormalities in temperature regulation and postural hypotension. Concentrations of HIAA and HVA in the CSF were very low. Serotonin in whole blood and catecholamines in plasma were also low. Elevated amounts of L-DOPA, 5-hydroxytryptophan (HTP) and 3-methoxytyrosine were found in the urine. The activity of AADC (Figure 17.1) was close to zero (1 percent of control) in plasma and liver.
Transdermal Absorption of L-Dopa from a New System Composed of two Separate Layers of L-Dopa and Hydrogel in Rats
Published in Drug Development and Industrial Pharmacy, 2000
Hiroaki Iwase, Jun-ichi Sudo, Jun Terui, Katsuhiko Kakuno, Takiko Watanabe, Kozo Takayama, Tsuneji Nagai
To maintain the stability of L-dopa in hydrogel, a new system composed of two separate layers of L-dopa and hydrogel was developed. L-Dopa sheets were made by immersing L-dopa solution into wiper sheets and by lyophilizing them. Examination for stability of L-dopa in the L-dopa sheet revealed that its stability was maintained for at least 12 weeks, providing the sheet was kept at room temperature in a dark box. In a cutaneous absorption study of L-dopa in rats, an L-dopa sheet was attached to the shaved abdominal skin. A hydrogel composed of cutaneous absorption enhancers, water and ethanol, was spread on vinyl tape (hydrogel sheet), and this sheet was placed over the L-dopa sheet. L-Dopa that was administered transdermally effectively penetrated through the skin: The plasma level of L-dopa peaked at 30 min and remained high between 60 and 180 min after the cutaneous application. Our system, composed of two separated layers of L-dopa and hydrogel, enabled the stability of L-dopa to be maintained without losing transdermal absorption of L-dopa.
Elevation of Plasma Levels of L-Dopa in Transdermal Administration of L-Dopa-Butylester in Rats
Published in Drug Development and Industrial Pharmacy, 2002
Jun-ichi Sudo, Hiroaki Iwase, Kimio Higashiyama, Katsuhiko Kakuno, Fumiji Miyasaka, Takashi Meguro, Kozo Takayama
ABSTRACT To increase delivery of L-dopa in its transdermal absorption, a new lipophilic derivative of L-dopa, L-dopa-butylester, was synthesized. An in-vitro study employing two-chamber diffusion cells, in which the excised rat abdominal skin was mounted, revealed that, in the presence of L-menthol and ethanol, L-dopa-butylester penetrated in its original form more effectively than L-dopa. L-Dopa-butylester sheets were made by immersing wiper sheets in methanol containing the compound, and then evaporating the methanol. An extraction study of the compound from the sheets revealed that its stability was maintained for at least 12 weeks. In an in-vivo cutaneous absorption study, an L-dopa-butylester sheet was attached to the shaved rat abdominal skin. A hydrogel containing L-menthol and ethanol was spread on vinyl tape, and this sheet was placed over it. In plasma, the L-dopa level rose linearly between 30 and 180 min after the cutaneous application; L-dopa-butylester was not detected. The L-dopa level was higher than that in which L-dopa was applied. These findings indicated that the lipophilic nature of L-dopa-butylester further increased its penetration through the skin, and that L-dopa-butylester that was taken up into the general circulation system was rapidly converted to L-dopa by hydrolysis in the body.
Changes in Chemical Structure and Biological Activity of L-DOPA as Influenced by an Andosol and Its Components
Published in Soil Science and Plant Nutrition, 2005
Syuntaro Hiradate, Akihiro Furubayashi, Yoshiharu Fujii
Velvetbean (Mucuna pruriens) has been reported to release 3-(3′,4′-dihydroxyphenyl)-L-alanine (L-DOPA) as an allelochemical that inhibits the growth of other plants, although the inhibitory activity depends on the soil type and it is extremely reduced in Andosols. To clarify the effects of Andosols and their components on the chemical structure and plant-growth-inhibitory activity of L-DOPA, an L-DOPA solution was reacted with an Andosol and its components (weathered pumice and purified allophane), and the resultant solution was subjected to 1H nuclear magnetic resonance and ultraviolet-visible spectral analyses, and plant-growth-inhibitory activity tests. When the L-DOPA solution was added to the soil components, the concentration of L-DOPA in the solution decreased by adsorption and transformation (polymerization) reactions. The adsorption mechanism included a ligand exchange reaction. The rate of L-DOPA transformation was faster at higher pH values. The soil components displayed a catalytic activity and accelerated the transformation of L-DOPA. Similar transformation occurred when light was irradiated. At pH values higher than 4.0, the transformed products from L-DOPA consisted of humic substances-like heterogeneous components, whereas specific components with low molecular weight were included when L-DOPA was transformed at a pH value of 9.7 or higher. The plant-growth-inhibitory activity of L-DOPA was extremely weakened when L-DOPA was adsorbed on or transformed (polymerized) by soil components. Therefore, in soils with high abilities of adsorption and transformation of L-DOPA such as in Andosols, it was likely that the L-DOPA concentration in the soil solution decreased quickly by adsorption and transformation reactions and the allelopathic activity of L-DOPA was lost.