membrane protein that uses ATP for active transport of out of or, in some cases, into the
cell. ABC transporters occur in human and microbial cells and may cause resistance to
chemotherapy in both
Transient depolarization (inversion) of the normally negative-inside electrical potential
across the cytoplasmic membrane, mediated by voltage-gated ion channels. Occurs only on
excitable cells
active metabolite
metabolic conversion product of a drug that retains pharmacological activity, or acquires
a novel one
adenylate cyclase
membrane-associated enzyme that converts ATP to the second messenger cAMP
adenylate kinase
enzyme that catalyzes the reversible reaction ATP+AMP ←→ 2 ADP
adrenal gland
endocrine gland that sits atop the kidney (which means there are two glands). The outer
layer, or cortex, produces various steroid hormones; the inner layer, or medulla, produces
epinephrine (adrenaline) and norepinephrine (noradrenaline)
adrenergic
literally: using adrenaline. The term is applied both to synapses that release adrenaline
(epinephrine) or noradrenaline (norepinephrine) and to receptors that are activated by
these transmitters. The terms ‘dopaminergic’, ‘cholinergic’ and so
forth are used analogously
adrenergic receptor
G protein-coupled receptor activated by adrenaline (epinephrine) or noradrenaline
(norepinephrine)
adrenocorticotropic hormone
peptide hormone secreted by the hypophyseal gland. Activates proliferation and hormone
production in the cortex of the adrenal glands
agonist
drug that activates its receptor
agonist-specific coupling
response of a receptor to an agonist that leads to preferential activation of one of its
downstream signaling cascades over the others
albumin
most abundant plasma protein. Produced in the liver; contributes prominently to the
osmotic activity of blood plasma and to the protein binding of drugs
alkaloid
secondary (that is, non-essential) metabolite of plant or microorganism, usually rich in
nitrogen, often poisonous
alkylating anticancer drugs
drugs that covalently react with DNA to introduce alkyl moieties into it. The term is
sometimes also loosely applied to drugs that cause other types of DNA modification. Active
on both dividing and resting cancer cells
allergy
Reaction of the specific immune system against drugs or other allergens such as pollen,
foodstuffs or microbial macromolecules leading to formation of allergen-specific
antibodies or lymphocytes and clinical symptoms upon repeated allergen exposure
allosteric
action mode of a drug that binds to a receptor outside of the regular ligand’s
binding site. The receptor can bind both the drug and the native ligand
α-motoneuron
a nerve cell that resides in the brain stem or spinal cord and controls, via its long
axon, a group of skeletal muscle cells
5-α-reductase
enzyme that reduces testosterone to the more potent androgen dihydrotestosterone.
Inhibitors are used therapeutically in prostate cancer
aminoglycosides
class of antibiotics that inhibit bacterial protein synthesis
analgesic
pain killer, pain-killing
androgens
steroid hormones that induce development and sustain function of male sexual organs and
body attributes. Testosterone and dihydrotestosterone are the most prominent androgens;
they are produced in the Leydig cells of the testicles
angina pectoris
intermittent of hypoxia and pain in the heart, usually caused by a combination of
atherosclerotic constrictions and vasospasms. Classical indication for nitroglycerin
treatment
antagonist
drug that inhibits its receptor
antidepressant
drug that counteracts the symptoms of depression, such as dark mood and lack of energy.
Typically used in depressive episodes of bipolar disease and in monopolar depression
antimetabolite
inhibitor of an enzyme that functions in a metabolic pathway
antimicrobial resistance
primary or secondary (acquired) insensitivity of pathogenic microbes to antimicrobial
chemotherapy
antisense oligonucleotide
a stretch of single-stranded DNA or RNA, typically 15–25 nucleotides in length, that
is complementary to some cellular or viral RNA molecule, and selectively interferes with
its function through base-pairing
antitarget
a macromolecule that is frequently involved in drug toxicity and therefore must be
specifically examined for susceptibility to novel compounds during drug development
anucleate
not possessing a cell nucleus
aorta
main artery of the systemic circulation. Emerges from the left heart; initially points
upward but then bends around to run downward along the spine
apoptosis
programmed cell death. Occurs during embryonic development, in pruning autoreactive
lymphocyte clones, and other physiological processes; can be triggered by radiation and
other causes of DNA damage
aptamer
DNA or RNA molecule that has been selected for affinity to a target molecule, which
usually is not a nuceic acid
aromatase
Enzyme of the cytochrome P450 family that introduces an aromatic ring into various
androgenic steroids and thereby converts them to estrogens. Inhibitors are used
therapeutically in gynecological tumors
l-aromatic amino acid transporter
transports aromatic amino acids—phenylalanine, tyrosine, tryptophan, but also the
prodrug l-DOPA—across cell membranes, including those at
the blood brain barrier
aromatic hydrocarbon receptor
nuclear receptor that, when bound to aromatic hydrocarbons, induces cytochrome P450 1A1
and other enzymes
arteriole
small artery
atherosclerosis
inflammatory and degenerative disease of the arteries. Promoted by high cholesterol and
blood pressure. Most common underlying cause of stroke and myocardial infarction, which
occur when blood clots form on top of atherosclerotic lesions
autoimmune disease
disease caused by formation of antibodies and/or T-lymphocytes that react with proteins or
other macromolecules of the body
functional part of the nervous system that is not under voluntary, conscious control.
Mainly concerned with regulation of circulation and interior organ function
axon
branched structure of nerve cell that conducts action potentials generated in this cell to
the synapses it forms with other nerve cells
basal membrane
thin layer composed of proteins and proteoglycans to which endothelial or epithelial cells
adhere. In capillaries and glomerular arterioles, the basal membrane functions as a
molecular sieve that restricts the movement of macromolecules
benign tumor
disinhibited growth of clonal cells that remains local and confined within a clear
anatomical boundary (often a connective tissue capsule). Most benign tumors are not
treated with drugs but are surgically removed. May progress to malignant tumor when left
untreated
β-arrestin
protein that binds to phosphorylated GPCRs. This inactivates the receptors and tags them
for endocytosis
β-lactam antibiotics
class of antibiotics that contain a reactive β-lactam ring and covalently inhibit
muramyl-transpeptidase. Comprises penicillins, cephalosporins, and carbapenems
β-lactamase
bacterial enzyme that cleaves the β-lactam ring of β-lactam antibiotics and in
this way inactivates them
conduit that drains the bile produced in the liver lobuli toward the small intestine. Also
connected to the bile bladder, which concentrates and stores surplus bile
biliary
involving or belonging to the bile or bile duct and bile bladder
blood brain barrier
functional and anatomical barrier that restricts permeation of many small solutes,
including drugs, from the circulation into the brain and spinal cord
blood coagulation
formation of blood clots. Involves activation both of the plasmatic cascade of coagulation
factors and of thrombocytes. Activated by contact of blood with matrix proteins or other
surfaces different from vascular endothelium, as induced by cuts or other lesions to the
blood vessels
blood plasma
The acellular fluid fraction of the blood, which makes up ~55% of the total blood volume.
Plasma still contains the proteins for clot formation (coagulation); in serum, these have
been removed
the acellular component of bone tissue. Composite material containing protein fibrils,
mostly collagen, and bone mineral, mostly hydroxyapatite. Produced by osteoblast cells,
dissolved by osteoclast cells
peptide hormone produced in the C-cells of the thyroid gland in response to high blood
calcium levels. Promotes mineral deposition in the bone matrix
calcitriol
major form of vitamin D. Precursor can be photochemically synthesized in the skin from
7-dehydrocholesterol. Increases intestinal uptake of calcium and phosphate
calcium channel
ion channel that selectively transports calcium
calmodulin
small regulatory protein that binds calcium and then associates with multiple
intracellular proteins to either activate or inactivate them
capillary
tiny blood vessels between arteries and veins. Substrate and gas exchange between
circulating blood and tissues occurs across their thin and porous walls
capsid
protein shell, usually of icosahedral symmetry, that encases the nucleic acids of a viral
genome. In naked viruses such as enteroviruses, the capsid forms the outermost layer; in
enveloped viruses, it is contained within a lipid membrane
Disturbance of heart rhythm, due to excessive activity, or lacking activity, of the
heart’s excitation-conduction system. Causes are diverse; often treated with drugs
that modulate ion channel function
catecholamine
this term comprises dopamine, norepinephrine, and epinephrine
blockade of an ion channel by a drug. Can take the shape of fast block, in wich a drug
binds reversibly within the conducting pathway of the channel, or as a slow block, in
which a drug binds and stabilizes the inactive channel conformation
inhibition by a drug that reversibly binds to a receptor or enzyme and displaces the
physiological ligand or substrate
complement system
a system of plasma proteins that participates in immune defense by facilitating
phagocytosis or by directly attacking the cell membranes of pathogenic microbes. Activated
by antibodies as well as by particles with non-physiological surface properties
cooperativity
synchronized ligand binding and conformational transition by the multiple subunits of an
oligomeric receptor or enzyme
coronary artery
artery that supplies the heart itself with blood. There are three major coronary arteries.
Occlusion of a coronary artery causes myocardial infarction
corticotropin releasing hormone
peptide hormone produced by the hypothalamus that activates the secretion of
adrenocorticotropic hormone (ACTH) from the hypophyseal gland
cyclical glucose polymers with 6–8 subunits. Useful for drug solubilization and
delivery
cyclooxygenase
enzyme that converts arachidonic acid to prostaglandin H2, a key intermediate
in the synthesis of other prostaglandins and of thromboxanes. Important drug target for
inhibiting inflammation, pain, and thrombocyte aggregation
cys-loop receptor family
homologous family of pentameric ligand-gated ion channels. Contains the GABAA
receptor and the nicotinic acetylcholine receptor as major drug targets
cystic fibrosis
genetic disease caused by a homozygous deficiency of a chloride transport protein
cytochrome P450
class of enzymes that perform a wide spectrum on oxidative reactions on both endogenous
metabolites and xenobiotics
dendrite
branched structure of a nerve cell that forms synapses with upstream nerve cells
metabolically inert glucose polymer produced by Leuconostoc
bacteria
diabetes mellitus
endocrine and metabolic disease caused by lack of insulin activity, either due to lack of
hormone, lack of tissue sensitivity to insulin, or excess activity of hormones
antagonistic to insulin
diaphorase
NADH-dependent redox enzyme that participates in reductive drug metabolism. Also referred
to as quinone reductase
differentiation
the acquisition of cell type-specific morphological and biochemical traits by cells
forming through division of undifferentiated stem cells. Often occurs successively during
multiple cell generations
diffusion potential
electrochemical that forms across membranes if these are selectively permeable toward an
ion species for which there is a concentration gradient across the membrane
uptake of a drug from the compartment of application (for example the digestive tract)
into the blood plasma
drug conjugation
Coupling of drug molecules with functional groups derived from cosubstrates. Usually
renders the drug less active, more polar, and more suitable for excretion
drug distribution
migration of the drug from the blood plasma to the rest of the organism
drug elimination
removal of the drug from the body through excretion with the urine or bile, often
subsequent to enzymatic modification
EC50
the concentration of a drug at which it exhibits 50% of its maximal effect
Edman degradation
experimental technique for protein sequence determination through successive removal of
single amino acids from the N-terminus
efficacy
strength of a drug’s functional effect at saturating concentrations
eicosanoids
class of mediators biosynthetically derived from arachidonic acid. Comprises
prostaglandins, leukotrienes, thromboxanes, lipoxins, and endocannabinoids
electrical synapse
a connection between two neighboring excitable cells, mostly in heart and smooth muscle,
that conducts ions and thereby allows action potentials to spread between the cells
encapsulation of a drug with an inert polymer that remains solid at the low pH in the
stomach but dissolves in the slightly alkaline milieu of the small intestine
entero-hepatic cycling
repeated biliary secretion and intestinal uptake of a drug molecule. Often also involves
repeated conjugation in the liver and deconjugation by bacterial enzymes in the large
intestine
epithelium
cell layer that grows atop a basal membrane. Assumes many different organ-specific shapes
and functions, such as selective solute transport in intestinal and kidney epithelia, and
metabolism and biosynthesis in liver epithelia
epoxide hydrolase
enzyme that hydrolyzes epoxide groups that may be introduced into xenobiotic molecules by
cytochrome P450
equilibrium potential
the voltage at which the driving forces associated with a diffusion potential are at
equilibrium
ergosterol
major sterol of fungal and some protozoal cell membranes. Drugs that bind ergosterol or
inhibit its synthesis are widely used in antifungal chemotherapy
estrogens
steroid hormones that induce development and sustain function of female sexual organs and
body attributes. Estradiol and estriol are the most prominent estrogens; they are produced
by the ovaries
population of specialized cells in the heart that spontaneously generate action potentials
and distribute them throughout the heart muscle. The system’s topmost part is the
sinoatrial node; it usually sets the heart rhythm
excitation-contraction coupling
the functional connection in a muscle cell between its excitation by action potentials and
its contraction
excitatory postsynaptic potential
localized, partial and short-lived depolarization of a postsynaptic membrane, caused by a
single firing of the presynaptic terminal
exocrine
(gland) secreting to the exterior. Also includes secretion across mucous membranes, for
example into the intestines
extracellular signal-regulated kinase
protein kinase that is activated downstream of various types of receptors. ERKs affect
transcription and cell proliferation
false transmitter
a drug that accumulates in presynaptic transmitter storage vesicles and thereby excludes
the true transmitter from storage and subsequent release
threshold voltage at which a voltage-gated channel will open. Usually below neutral, but
differs substantially between different channels
first pass effect
extent of metabolic inactivation of a drug as it passes through the liver immediately
after intestinal uptake. Commonly stated as percentage of the total
fluorescence resonance energy transfer
(FRET) nonradiative transfer of excitation energy between two fluorophores. The emission
spectrum of the donor fluorophore must overlap the absorption spectrum of the acceptor
fluorophore. FRET occurs over distances of no more than a few nanometers, which makes it
useful for studying binding and dissociation of proteins
follicle-stimulating hormone
hypophyseal peptide hormone that stimulates ovary follicle development in women and
spermatogenesis (sperm cell formation) in men
receptor protein in the cytoplasmic membrane that binds a ligand on the extracellular side
and then activates a heterotrimeric G protein on the intracellular side
GABAA receptor
ligand-gated chloride channel in the brain that is activated by GABA (γ-aminobutyric
acid). Inhibits neuronal excitation; major drug target
genetic knockout
inactivation of a specific gene using recombinant DNA techniques. Widely used in
experimental cell biology and for target validation in drug discovery
glaucoma
eye disease characterized by excessive pressure within the eye; can lead to blindness in
extreme cases
glia cell
cell in brain tissue that is not a nerve cell. Among the various types of glia cells,
astrocytes are the most common ones
steroid hormones that affect metabolic regulation and inhibit inflammation. Produced in
the adrenal gland; cortisol and cortisone are the most important of these hormones
glucose-6-phosphate dehydrogenase
first enzyme in the hexose monophosphate shunt. Mutations of this enzyme cause lack of
NADPH in erythrocytes and favism
glutathione-S-transferase
enzyme that couples free glutathione to an electrophilic center on a substrate molecule,
most commonly a xenobiotic
Equation that relates the magnitudes of multiple ion gradients across a membrane to the
overall diffusion potential. Generalization of the Nernst equation
gonadal
relating to the gonads, that is, the ovaries and testicles
protein kinase that phosphorylates activated GPCRs and thereby primes them for
inactivation by β-arrestin
Gram-negative
class of bacteria with cell walls that have an outer membrane containing
lipopolysaccharide
Gram-positive
class of bacteria, characterized by a comparatively simple cell wall structure that lacks
an outer membrane
green-fluorescent protein
protein, isolated originally from a jellyfish species, which autocatalytically forms an
internal fluorophore that emits visible (green) light. Translational fusion with GFP, or
mutant variants thereof, is widely used in experimental cell biology to track proteins of
interest
growth hormone
hypophyseal peptide hormone that promotes production of growth factors in several tissues.
Promotes growth, raises blood glucose
protein that causes clumping (agglutination) of red blood cells. The hemagglutinins of
influenzavirus and related viruses bind neuraminic acid residues on cell surfaces,
including those of red blood cells; this causes cell clumping because one virus particle
contains multiple copies of the hemagglutinin protein and thus can bind to multiple cells
hemodynamic shock
acute drop of blood pressure, usually accompanied with counterregulatory rise of the heart
rate. Major causes are blood volume loss, vasodilation in septicemia, or acute heart
muscle failure in myocardial infarction
hemolytic anemia
lack of red blood cells due to their premature destruction. In the context of
pharmacology, most commonly triggered by drugs in conjunction with glucose-6-phosphate
dehydrogenase deficiency (favism)
hepatic
concerning or belonging to the liver
Her2/neu
growth factor receptor. Excessive activation promotes growth of breast cancer and some
other cancers. Therapeutically targeted with inhibitory monoclonal antibodies
HMG-CoA reductase
key enzyme in the biosynthesis of cholesterol. Converts hydroxymethylglutaryl-CoA
(HMG-CoA) to mevalonic acid. Inhibited by “statin” drugs
humanized antibody
hybrid monoclonal antibody that combines a mouse-derived antigen recognition site with a
human antibody scaffold. Less immunogenic in humans than conventional mouse-derived
monoclonal antibodies
hyperpolarization
deviation of the membrane potential from its normal value to a more strongly negative
(inside) value
hypertension
pathologically increased arterial blood pressure
hypertensive crisis
a medical emergency, typically occurring in patients with known chronic hypertension,
characterized by spiking yet rapidly changing arterial blood pressure
hypophyseal gland
small endocrine gland connected to the hypothalamus that secretes multiple peptide
hormones, many of which control other endocrine glands
hypothalamus
portion of the brain located close to the brain stem. It is anatomically and functionally
connected to the hypophyseal gland and controls many activities of the autonomic nervous
system
inferior vena cava
major vein that collects all venous blood from the entire body below the heart. There is a
superior vena cava as well that drains venous blood from the upper part of the body
inhibitory postsynaptic potential
localized and short-lived hyperpolarization of a postsynaptic membrane, caused by a single
firing of a presynaptic terminal that releases an inhibitory transmitter
inositoltriphosphate
second messenger released from phosphatidylinositol-bis-phosphate by phospholipase C.
Activates a cognate receptor in the endoplasmic reticulum that is a calcium channel
interstitial space
the entirety of the fluid-filled extracellular space outside of the circulation
intravascular
within the blood vessels
inverse agonist
an inhibitory drug that reduces the activity of its receptor to a level below that of the
unbound state
ion channel
membrane protein that selectively conducts one or several specific ion species
ionophore
small molecule that reversibly binds specific ions; the bound complex is able to
efficiently cross cell membranes
inhibition by a drug that binds irreversibly, usually by forming a covalent bond, to a
receptor or enzyme and displaces the physiological ligand or substrate
KATP channel
ATP-regulated potassium channel
lead compound
molecule that binds and acts on a given drug target that serves as the starting point for
drug development, which usually involves increasing affinity and improving pharmacokinetics
leak channels
ion channels that are continually open. K+ leak
channels are important in stabilizing the resting potential in human cells
leukemia
malignancy derived from any of the cell lines of the bone marrow. Grows diffusely in the
bone marrow and, in advanced cases, in the liver and spleen. Mostly treated with
chemotherapy
leukocytes
white blood cells. Consist of granulocytes, lymphocytes, and monocytes
leukotrienes
class of eicosanoids involved in inflammation and allergy
ligand-gated ion channel
ion channel that opens—or, in some cases, closes—in response to the binding of
a ligand molecule. The ligand may bind from the extracellular side, as is the case with
neurotransmitter receptors, or from the intracellular side, which happens with cyclic
nucleotide-gated (CNG) channels
lipopeptide
a peptide that is modified with a fatty acyl residue. Many lipopeptides are antibiotics
lipopolysaccharide
key component of the outer membrane of Gram-negative bacteria. Consists of a core
oligosacharide carrying 6–7 fatty acyl residues, as well as a typically very long
linear polysaccharide chain. Powerful trigger of non-specific immune reactions
liposomes
artificial membrane vesicles, consisting of a lipid bilayer that encloses an aequeous
interior volume
plasma lipoprotein species rich in cholesterol. Forms from very low density lipoprotein
(VLDL) through extraction of triacylglycerol by lipoprotein lipase
luteinizing hormone
hypophyseal peptide hormone that stimulates ovulation and progestin formation in women and
androgen formation in men
lysosome
specialized cellular vesicle carrying hydrolytic enzymes and other molecules that aid in
the inactivation and degradation of phagocytosed microbes and particles
infectious disease caused by the unicellular eukaryotic parasite Plasmodium falciparum and related species, and transmitted by Anopheles mosquitoes. Parasites propagate in red blood cells and
sometimes in the liver
malignancy
behavior of tumors, characterized by genetic instability, local invasiveness, and
metastasis formation
malignant lymphoma
cancer derived from lymphatic cells. Multiple forms; major distinction according to
B-cells or T-cells. May grow as a single solid tumor mass or diffusely. Typically treated
with radiation or chemotherapy, not surgery
membrane potential
electrical potential across the cell membrane, caused by ion concentration gradients
across and ion channels within the membrane. Most often on the order of −60 to
−70 mV inside relative to outside
metastasis
(pl. metastases) secondary tumor. Arises from single cells that are released by the
primary tumor and carried with the blood, lymph or otherwise to remote locations, where
they settle and proliferate. Formation of metastases is a hallmark of malignant tumors
mineralocorticoids
steroid hormones that promote excretion of K+ and
retention of Na+. Produced in the adrenal gland;
aldosterone is the most important such hormone
monoamine oxidase
enzyme involved in the oxidative degradation of monoamine transmitters, and also in the
metabolism of some drugs
monoamine transmitter
this term comprises catecholamines, serotonin, and histamine
motor endplate
synapse between a motoneuron and skeletal muscle cell
cholinergic G protein-coupled receptor. Multiple subtypes, occurs mostly in the
parasympathic nervous system
muscle relaxant
drug that induces muscle relaxation by blocking synaptic transmission in the motor
endplate
myasthenia gravis
autoimmune disease. Autoantibodies directed at the nicotinic acetylcholine receptor in
motor endplates compromise synaptic transmission, resulting in muscle weakness
mycobacteria
class of bacteria with thick, multilayered cell walls. Includes causative agents of
tuberculosis and leprosy
mycolic acid
fatty acid with very long alkyl chain found in mycobacterial cell walls
myocardial infarction
acute occlusion of a coronary artery caused by a blood clot, typically atop an
atherosclerotic lesion, with subsequent degeneration of the part of the heart muscle that
has been deprived of perfusion
nephron
functional unit of the kidneys. Consists of a glomerulus that produces primary filtrate
from blood plasma and of several successive tubular segments that post-process the
filtrate into urine
Nernst equation
equation that relates the magnitude of an ion gradient across a membrane to the resulting
diffusion equilibrium potential
neuron
nerve cell
neurotransmitter
small molecule that is released by a nerve cell and activates or inhibits another nerve
cell or other excitable cell nearby
neutral antagonist
a drug that neither increases nor decreases the activity of its receptor relative to the
receptor’s unbound state
nicotinic acetylcholine receptor
ligand-gated cation channel that is activated by acetylcholine and causes cell excitation.
Found in motor endplates, autonomic ganglia, and the brain
nitric oxide synthase
enzyme that produces NO from arginine, using NADPH and O2 as cosubstrates. Occurs in three isoforms, namely
endothelial NOS, neuronal NOS, and inducible NOS
non-ionic diffusion
The transport across membranes of an ionizable drug molecule in its non-ionized form
nuclear hormone receptor
receptor protein that binds a hormone or metabolite and then binds to cognate DNA
sequences and regulates gene transcription through transactivation or transrepression. In
transactivation, hormone-bound receptors act as transcription factors, that, is they bind
to cognate DNA motifs and induce gene transcription. In transrepression, hormone-bound
receptors interact directly with other transcription factors and prevent them from binding
to DNA. Nuclear hormone receptors mediate the effects of steroids, thyroid hormones, and
retinoic acid, as well as enzyme induction in drug metabolism
oncoprotein
mutant protein (encoded by a corresponding oncogene) that
initiates or sustains malignant behavior of tumor cells
organic anion transporter
class of transport protein important in drug transport; operates either by facilitated
diffusion or secondary active transport
organic cation transporter
class of transport protein important in drug transport; operates either by facilitated
diffusion or secondary active transport
orphan receptor
putative receptor protein, identified as such by sequence homology to known receptors,
with as yet unknown ligand and function
orthosteric
binding mode of a drug that binds “in the right place”, i.e. within the same binding pocket that is also used by a
receptor’s physiological ligand. The receptor can therefore only bind either its
physiological ligand or the drug, not both
part of the autonomic nervous system. Lowers the heart rate and blood pressure, promotes
interior organ perfusion and function. Transmission prominently mediated by acetylcholine.
Antagonistic to the sympathetic
nervous system
peptide hormone produced by the parathyroid glands, which are four small nodes of gland
tissue attached to the thyroid gland. Mobilizes calcium and phosphate from bone matrix and
increases their resorption in kidneys and intestine
Parkinson’s disease
CNS disease with motor symptoms, caused by degeneration of dopamine-producing cells in the
brain stem
partial agonist
a drug that increases the activity of its receptor to a level above that of the unbound
state but below that achieved by a full
agonist
patch clamp technique
experimental setup to study the conductivity of ion channels in small numbers or singly on
live cells
pathogenesis
the biochemical or physiological mechanism by which the ultimate cause of a disease causes
its clinical manifestations
matrix material of the bacterial cell wall, consisting of linear strands of
N-acetylglucosamine and muramic acid that are crosslinked by oligopeptides; crosslinks are
formed extracellularly by muramyl-transpeptidase
uptake of particles by cells, mostly specialized phagocytes such as neutrophil
granulocytes and macrophages. After uptake, the particles are enclosed, and often
destroyed, within phagosomes. Important part of immune defence against bacteria and fungi
as a solitary term: general principles of drug action; when applied to a specific drug:
that drug’s mode of action
pharmacokinetics
study of drug movement and turnover, that is, rates and mechanisms of uptake into,
distribution within and elimination from the body. When applied to a single drug, denotes
that drug’s characteristics of uptake, distribution, and elimination
pharmacology
scientific discipline concerned with the modes of action and therapeutic uses of drugs
pharmacophore
consensus set of molecular properties such as charge distribution and shape required for
activation or inhibition of a specific drug target
pharmacotherapy
medical treatment using drugs
phase I metabolism
initial reaction in the metabolic transformation of a drug. Often performed by cytochrome
P450 enzymes
phase II metabolism
conjugation of a drug that involves a reactive site on the drug molecule that was created
or exposed in a phase I reaction. Typically consists in conjugation with a polar moiety
that facilitates excretion
phase III metabolism
a bit of a misnomer; denotes no actual chemical reaction but excretion of drug
metabolites. The transporters that mediate excretion often recognize substrates that are
conjugated with glucuronic acid and glutathione
phenotypic screening
strategy for drug discovery in which the desired functional response of a cell or organism
is observed directly after application of each candidate drug, and the search is not
limited to a specific molecular target
phosphodiesterase
enzyme that inactivates cAMP or cGMP by cleaving them to AMP or GMP, respectively. Several
isoforms differ in preference for one or the other cyclic nucleotide
phospholipase A2
enzyme that cleaves the fatty acyl residue connected to the second (central) carbon of the
glycerol backbone
phospholipase C
enzyme that cleaves the headgroup, including the phosphate, from a phospholipid substrate,
leaving diacylglycerol in the membrane
photoaffinity labeling
experimental technique for identifying binding sites of specific ligands
physiology
scientific study of the physical and chemical principles of organ function
class of antibiotics that contain an extended polyene moiety and bind to ergosterol or
other sterols in cell membranes
polyprotein
translation product that is destined to be proteolytically cleaved into multiple
functionally unconnected proteins. Many viruses, including HIV and hepatitis C virus,
encode polyproteins and a protease that processes it
portal circulation
the part of the circulation that involves the portal vein. Venous blood from the
intestinal organs, the spleen, and the pancreas is drained into the portal vein and passed
through the liver before reentering the general circulation
drug precursor molecule that must undergo metabolic transformation in order to become
activated
progestins
class of steroid hormones that maintain the mucous membrane of the uterus in a state ready
for accepting the fertilized egg cell, and sustain the function of the placenta throughout
pregnancy. Produced in the ovaries and, during pregnancy, the placenta itself
class of eicosanoids involved in pain perception, inflammation, blood coagulation, and
other physiological and pathological phenomena
protease-activated receptors
GPCRs that are activated by proteolytic cleavage, rather than by binding of an extrinsic
ligand
protein binding
nonspecific adsorption of drugs to proteins, most prominently albumin and other plasma
proteins
protein phosphorylation
transfer of a phosphate group from ATP or GTP to a substrate protein by a protein kinase.
Usually results in either activation or inactivation of the substrate protein. Can be
undone by protein phosphatases
protozoa
taxonomic category that includes single-celled, eukaryotic pathogens. Phylogenetically
heterogeneous
radicalic or ionic oxygen species or oxygen compounds. Important examples are O2− and H2O2. May arise as side products in normal
metabolism, through ionizing radiation, or be formed by dedicated enzymes that are
particularly abundant in phagocytes. Important for immune defense but also involved in
tissue destruction in inflammatory diseases
receptor
macromolecule that is bound and activated, inhibited, or otherwise functionally influenced
by a drug or other ligand. Note that this definition excludes proteins such as albumin
that merely bind drugs but are not functionally affected by them
receptor desensitization
inactivation of a receptor in response to prolonged exposure to ligand
receptor occupancy
fraction (percentage) of a receptor that is
saturated with a cognate drug or ligand
receptor tyrosine kinase
a receptor that is also a protein kinase. Binding of the hormone or other mediator to the
receptor activates the kinase activity, which attaches phosphate to tyrosine residues on
substrate proteins
refractory state
functional state of a receptor molecule, or of a cell, in which it is inactive and at the
same time not amenable to activation
renal
concerning or belonging to the kidneys
renal clearance
parameter that governs the renal elimination of a drug; defined as volume flow of urine
times urine concentration over plasma concentration of the drug
resorption ester
a prodrug in which a polar moiety such as a carboxyl or hydroxyl group has been converted
to an ester, so as to make the molecule less polar and improve its intestinal absorption
resting potential
membrane potential in excitable cells that prevails in the absence of action potentials
retinoid X receptor
nuclear hormone receptor that binds retinoic acid and, after forming a heterodimer with of
of several other receptors, affects gene transcription
rheumatism
group of autoimmune diseases affecting the joints and sometimes other organs
rhodopsin
light-activated GPCR that acts as the light sensor in the eye
RNA interference
Sequence-specific inhibition of gene expression at the level of mRNA, induced by
double-stranded RNA sequences
ryanodine receptor
a calcium-activated calcium channel in the endoplasmic reticulum. Involved in
excitation-contraction coupling in muscle cells
salvage pathway
metabolic pathway that diverts purine and pyrimidine bases or nucleosides from complete
degradation and converts them back to intact nucleotides
sarcoma
malignant tumor derived from non-epithelial tissues such as bones, cartilage and muscle
Scatchard plot
a plot format for ligand binding data that is useful for distinguishing single from
multiple binding sites
second messenger
signaling molecule that is formed intracellularly downstream of the activation of a
hormone or neurotransmitter receptor.
Usually regulates multiple proteins in the cell. Examples: cAMP, cGMP, IP3
selective toxicity
toxic action of a drug that is limited to pathogenic microbes or to tumor cells
semisynthesis
organic-synthetic process that starts with a complex molecule obtained from some
biological source, typically a plant or microbe. This approach may be used for economical
reasons even if the target product can in principle be synthesized from scratch
septicemia
severe infection, in which the bacterial or fungal pathogen is carried in the bloodstream
and may settle in multiple organs. Often leads to septic shock, which is one form of
hemodynamic shock
muscle tissue with cells that lack the characteristic striated pattern found in skeletal
and heart muscle. Smooth muscle is always controlled by the autonomic nervous system
sodium channel
ion channel that selectively transports sodium. Activated by membrane depolarization
sodium-potassium ATPase
ATP-dependent membrane transporter that exchanges two extracellular K+ ions for 3 intracellular Na+ sodium ions; plays a key role in maintaining ion
gradients and membrane potential
soluble guanylate cyclase
cytosolic enzyme that converts GTP to the second messenger cyclic GMP (cGMP). Activated by
nitric oxide
spatial summation
cumulative depolarization of a postsynaptic membrane by simultaneous activity in several
adjoining synapses
part of the autonomic nervous
system. Increases heart rate and blood pressure, inhibits interior organ perfusion.
Uses both acetylcholine and norepinephrine as transmitters. Antagonistic to the parasympathetic nervous
system
synapse
connection between two nerve cells or other excitable cells. Transmitter is released from
the presynaptic nerve terminal into the synaptic cleft and binds to receptors on the
postsynaptic cell, which either increases or decreases its membrane potential. The
transmitter is inactivated by degradation or reuptake into the presynaptic cell
tachyphylaxis
rapid, usually partial desensitization of a receptor in response to sustained stimulation
by an agonistic drug
target validation
experimental evaluation of a hypothetical drug target by means of surrogate stimulation or
inhibition, often by means of genetic knockout or RNA interference
temporal summation
cumulative depolarization of a postsynaptic membrane by a rapid succession of excitatory
postsynaptic potentials occurring in the same synapse
therapeutic index
ratio of a drug’s toxic concentration over its therapeutic concentration
small enzyme molecule that reduces multiple substrates, including xenobiotics and
disulfide bonds in proteins. Contains two vicinal cysteine residues in the active site,
which are converted to a disulfide in the reaction and subsequently reduced again at the
expense of NADPH
thrombocytes
also called blood platelets. Small, anucleate
cells that are formed in the bone marrow as cytoplasmic fragments pinched off from
megakaryocytes. Play a key role in blood coagulation
thromboxanes
class of eicosanoids involved in blood coagulation and inflammation
thyroid gland
endocrine gland located in the front of the neck that produces thyroid hormones
(thyroxine, triiodothyronine) and calcitonin
key enzyme for hormone production in the thyroid gland
thyroid-stimulating hormone
hypophyseal peptide hormone that stimulates proliferation and hormone secretion in the the
thyroid
thyrotropin-releasing hormone
hypothalamic peptide hormone that stimulates the secretion of thyroid-stimulating hormone
from the hypophyseal gland
tight junction
complex protein structure that tightly connects the cytoplasmic membranes of two
neighboring cells in an endothelial or epithelial cell layer and restricts the passage of
fluid between the them
protozoal parasites, causative agents of sleeping sickness and Chagas disease
tubular secretion
active transport of solutes into the nascent urine. Occurs mostly in the proximal tubule
of the nephron
two-state model of receptor activation
theoretical model of receptor behavior. The receptor is assumed to spontaneously alternate
between an active and an inactive conformation. Agonists selectively bind and stabilize
the active conformation, antagonists selectively bind the inactive conformation
widening of blood vessels, caused by relaxation of vascular smooth muscle cells
(vasorelaxation). Excessive systemic vasodilation occurs can lead to hemodynamic shock
vasopressin
hypophyseal peptide hormone involved in regulating blood pressure and urine volume
venule
small vein
viral protease
virus-encoded protease that cleaves a viral polyprotein precursor to mature, functional
proteins
voltage-gated ion channel
ion channel that is opened in response to membrane depolarization
volume of distribution
ratio of the number of molecules of a drug in the body, divided by the plasma
concentration of this drug
xanthine oxidase
enzyme that oxidizes hypoxanthine to xanthine and then uric acid in the degradation
pathway for adenine and guanine. Also contributes to the metabolism of some drugs
xenobiotic response element
regulatory DNA sequence motif recognized by the pregnane X receptor
xenobiotics
small molecules that originate outside the human body and are not required in human
metabolism. The term includes drugs, poisons and inert substances, of both natural and
synthetic origin