3,4-Dihydroxyphenylacetic Acid
A deaminated metabolite of LEVODOPA.
Homovanillic Acid
Homovanillic acid (HVA) is a major metabolite of dopamine, formed in the body through the catabolic breakdown of this neurotransmitter by the enzyme catechol-O-methyltransferase and then further metabolized in the liver before excretion in urine.
Phenylacetates
Derivatives of phenylacetic acid. Included under this heading are a variety of acid forms, salts, esters, and amides that contain the benzeneacetic acid structure. Note that this class of compounds should not be confused with derivatives of phenyl acetate, which contain the PHENOL ester of ACETIC ACID.
Dopamine
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
Biogenic Monoamines
Homogentisic Acid
Hydroxyindoleacetic Acid
Hydroxyindoleacetic acid (5HIAA) is a major metabolite of serotonin, a neurotransmitter, formed by the action of monoamine oxidase and aldehyde dehydrogenase, and its measurement in urine is often used as a biomarker for serotonin synthesis in clinical and research settings.
Cycloparaffins
Alicyclic hydrocarbons in which three or more of the carbon atoms in each molecule are united in a ring structure and each of the ring carbon atoms is joined to two hydrogen atoms or alkyl groups. The simplest members are cyclopropane (C3H6), cyclobutane (C4H8), cyclohexane (C6H12), and derivatives of these such as methylcyclohexane (C6H11CH3). (From Sax, et al., Hawley's Condensed Chemical Dictionary, 11th ed)
Dihydroxyphenylalanine
A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.
Biogenic Amines
A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g., histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology.
Levodopa
The naturally occurring form of DIHYDROXYPHENYLALANINE and the immediate precursor of DOPAMINE. Unlike dopamine itself, it can be taken orally and crosses the blood-brain barrier. It is rapidly taken up by dopaminergic neurons and converted to DOPAMINE. It is used for the treatment of PARKINSONIAN DISORDERS and is usually given with agents that inhibit its conversion to dopamine outside of the central nervous system.
Corpus Striatum
Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.
Benserazide
An inhibitor of DOPA DECARBOXYLASE that does not enter the central nervous system. It is often given with LEVODOPA in the treatment of parkinsonism to prevent the conversion of levodopa to dopamine in the periphery, thereby increasing the amount that reaches the central nervous system and reducing the required dose. It has no antiparkinson actions when given alone.
Nomifensine
An isoquinoline derivative that prevents dopamine reuptake into synaptosomes. The maleate was formerly used in the treatment of depression. It was withdrawn worldwide in 1986 due to the risk of acute hemolytic anemia with intravascular hemolysis resulting from its use. In some cases, renal failure also developed. (From Martindale, The Extra Pharmacopoeia, 30th ed, p266)
Microdialysis
A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane.
Vanilmandelic Acid
Vanilmandelic acid (VMA) is a major metabolite of catecholamines, specifically normetanephrine and metanephrine, which are produced by the adrenal gland and can be measured in urine to help diagnose pheochromocytoma or neuroblastoma.
Brain Chemistry
Methoxyhydroxyphenylglycol
Synthesized from endogenous epinephrine and norepinephrine in vivo. It is found in brain, blood, CSF, and urine, where its concentrations are used to measure catecholamine turnover.
Dialysis
Pargyline
A monoamine oxidase inhibitor with antihypertensive properties.
Monoamine Oxidase Inhibitors
Serotonin
A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.
Tyrosine 3-Monooxygenase
Probenecid
The prototypical uricosuric agent. It inhibits the renal excretion of organic anions and reduces tubular reabsorption of urate. Probenecid has also been used to treat patients with renal impairment, and, because it reduces the renal tubular excretion of other drugs, has been used as an adjunct to antibacterial therapy.
Monoamine Oxidase
An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4.
Lobeline
Haloperidol
A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)
Chromatography, High Pressure Liquid
Norepinephrine
Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic.
Aromatic-L-Amino-Acid Decarboxylases
An enzyme group with broad specificity. The enzymes decarboxylate a range of aromatic amino acids including dihydroxyphenylalanine (DOPA DECARBOXYLASE); TRYPTOPHAN; and HYDROXYTRYPTOPHAN.
Tyramine
An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems.
Electrochemistry
Oxidopamine
Nucleus Accumbens
Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.
Neostriatum
The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.
Hypothalamus
Reserpine
An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.
Substantia Nigra
Rats, Sprague-Dawley
Methamphetamine
Rats, Inbred Strains
Epinephrine
The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.
Rats, Wistar
Neurotransmitter Agents
Substances used for their pharmacological actions on any aspect of neurotransmitter systems. Neurotransmitter agents include agonists, antagonists, degradation inhibitors, uptake inhibitors, depleters, precursors, and modulators of receptor function.
Brain
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Extracellular Space
Interstitial space between cells, occupied by INTERSTITIAL FLUID as well as amorphous and fibrous substances. For organisms with a CELL WALL, the extracellular space includes everything outside of the CELL MEMBRANE including the PERIPLASM and the cell wall.
Parkinson Disease
A progressive, degenerative neurologic disease characterized by a TREMOR that is maximal at rest, retropulsion (i.e. a tendency to fall backwards), rigidity, stooped posture, slowness of voluntary movements, and a masklike facial expression. Pathologic features include loss of melanin containing neurons in the substantia nigra and other pigmented nuclei of the brainstem. LEWY BODIES are present in the substantia nigra and locus coeruleus but may also be found in a related condition (LEWY BODY DISEASE, DIFFUSE) characterized by dementia in combination with varying degrees of parkinsonism. (Adams et al., Principles of Neurology, 6th ed, p1059, pp1067-75)