UNIDAD 4 :

Farmacodinamia

La farmacodinamia estudia las acciones y los

efectos de los fármacos.
“Mecanismos de acción y relación entre la
concentración y el efecto de los fármacos.”
Relación entre la concentración del fármaco y el
efecto
Sites at
which
drugs act
to
modify
cell
function
Sites at
which
drugs act
to modify
cell
function
Dose-frequency relationship
Measurement of binding (B) as a
function of concentration (c)
Concentration-binding relationship
Effect of substrate concentration on the initial velocity of
an enzyme-catalyzed reaction
 Vmax is extrapolated from
the plot, because V0
approaches but never quite
reaches Vmax. The
substrate concentration at
which V0 is half maximal is
Km, the Michaelis constant.
The concentration of
enzyme in an experiment
such as this is generally so
low that [S] [E] even when
[S] is described as low or
relatively low. The units
shown are typical for
enzyme-catalyzed reactions
and are given only to help
illustrate the meaning of V0
and [S]. (Note that the
curve describes part of a
rectangular hyperbola, with
one asymptote at Vmax. If
the curve were continued
below [S] 0, it would
approach a vertical
asymptote at [S]Km.)
Concepto de fármaco agonista y
antagonista
La capacidad del fármaco para modificar el receptor e iniciar
una acción es lo que define su eficacia.
El fármaco que presenta esta característica es denominado
agonista y el que no la presenta, es decir, que se une al
receptor, pero no lo activa, antagonista.
Con frecuencia, pequeños cambios en la estructura de un
fármaco modifican su eficacia; por esta razón, dentro de una
familia farmacológica, unos pueden tener propiedades
agonistas y otros, antagonistas.
Molecular mechanisms of drug-
receptor interaction
Potency and Efficacy of agonists
Curvas de Dosis - Respuesta
Afinidad: capacidad de un fármaco de unirse a su
receptor. Cuanto más próxima esté al eje Y, mayor es
la afinidad.
Potencia: la dosis relativa de dos o más agonistas que
producen el mismo efecto. Cuanto más próxima esté
al eje Y, mayor es la potencia.
Eficacia: es una medida del grado de respuesta que
produce el fármaco. Cuanto mayor sea la altura que
alcance, mayor es la eficacia.
Comparison
of 2 drugs
acting on
the Same
Receptor
Comparison of 2 drugs acting on Different Receptors
Parciales
Competitive antagonism
Antagonistas y Sinergicos
Duality of Partial Agonists
Toxicity and the Therapeutic Index
 1. Se presenta una gráfica de Dosis / Respuesta de dos drogas diferentes, A y B. Respecto a la gráfica, se puede
afirmar que:
a. la droga A posee un índice terapéutico (o ventana terapéutica) más amplio que la droga B
b. la dosis de la droga A requerida para alcanzar una respuesta terapéutica de 100% será tóxica en el 50% de los
pacientes.
c. la dosis de la droga B requerida para alcanzar una respuesta terapéutica de 100%, es la misma que la requerida
para la droga A para el mismo propósito
d. la droga A es más segura que la droga B
e. con los datos proporcionados no se puede realizar ninguna comparación entre los dos medicamentos
 2. Se presenta una gráfica de Dosis / Respuesta de dos drogas diferentes, A y B. Respecto a la
gráfica, se puede afirmar que:
a. la droga A posee un índice terapéutico (o ventana terapéutica) más amplio que la droga B
b. la dosis de la droga A requerida para alcanzar una respuesta terapéutica de 100% será tóxica en el
50% de los pacientes.
c. la dosis de la droga B requerida para alcanzar una respuesta terapéutica de 100%, es la misma que
la requerida para la droga A para el mismo propósito
d. como es una escala logarítmica, la dosis real de la droga B requerida para alcanzar una respuesta
terapéutica de 100% es el doble de la requerida para alcanzar el 10%
e. con los datos proporcionados no se puede realizar ninguna comparación entre los dos
medicamentos
Adverse drug effect: overdosing
Adverse drug effect: increased sensitivity

Intolerancia: Respuesta Exagerada a una dosis habitual.

Modificación Cuantitativa.
Idiosincracia: Respuesta Anormal pero en forma Cualitativa,
Diferente a la esperada. Aparece en forma precoz.
Adverse drug effect: lacking selectivity
Reacciones adversas Inmunológicas a Fármacos
Desensibilización de receptores
Es la pérdida de respuesta de una célula a la acción de un
ligando, como resultado de la acción de este ligando sobre la
célula.
La desensibilización determina que la célula quede
protegida frente a la estimulación excesiva o prolongada.
Cuando se desarrolla de manera rápida, se la denomina
también tolerancia aguda o taquifilaxia, y si lo hace de forma
lenta en el curso de días, tolerancia crónica.
Classes of Hormones
We recognize that each tissue and, more generally,
each cell of the organism secretes . . . special products
or ferments into the blood which thereby influence all
the other cells thus integrated with each other by a
mechanism other than the nervous system.
—Charles Édouard Brown-Séquard and J. d’Arsonval,
article in Comptes Rendus de la Société de Biologie,
1891
Reasons for different pharmacological
properties of enantiomers
Tipos de Receptores
Receptors Linked Via Coupling Proteins to Intracellular Effectors
Gs Proteins
Catecholamines (beta), dopamine (D1), glucagon, histamine
(H2), prostacyclin, and some serotonin subtypes.
Gi Proteins
adrenoreceptors (alpha,), ACh (M2), dopamine (D2 subtypes),
and several opioid and serotonin subtypes.
Gq Proteins
ACh (M1 and M3), norepinephrine (alpha 1), angiotensin II, and
several opioid and serotonin subtypes.
Membrane Receptors Directly Coupled to Ion Channels
Nicotine receptor for Ach, GABA A receptor.
Intracellular Receptors
Steroids, thyroid hormones, gonadal steroids, and vitamin D.
Tipos de Receptores
Cyclic CMP and Nitric Oxide Signaling
H1 and M3
Receptors That Function as Enzymes or Transporters
Inhibitors of acetylcholinesterase, angiotensin converting
enzyme, aspartate protease, carbonic anhydrase,
cyclooxygenases, dihydrofolate reductase, DNA/RNA
polymerases, monoamine oxidases, Na/K-ATPase,
neuraminidase, and reverse transcriptase.
Examples of drug action on transporter systems include the
inhibitors of reuptake of several neurotransmitters, including
dopamine, GABA, norepinephrine, and serotonin.
Receptors That Function as Transmembrane Enzymes –Tyrosine
kinase
Insulin and growth factors, including epidermal growth factor
(EGF) and platelet-derived growth factor (PDGF).
Receptors for Cytokines
Erythropoietin, somatotropin, and interferons.
Cytoplasmic tyrosine kinases (Janus kinases [JAKs]).
Six general types of signal transducers
Sistemas de 2do. Mensageros
G-Protein-coupled receptor
Ligand-
gated ion
channel
Protein synthesis-regulating receptor
Ligand-
regulated
enzyme
Classes and functions of selected G proteins
G-protein-linked 2nd messengers
Some Signals Transduced by G Protein–Coupled
Serpentine Receptors
Transduction of the epinephrine
signal: the adrenergic pathway
Interaction
of Gs with
adenylyl
cyclase
 The soluble catalytic
core of the adenylyl
cyclase (AC, blue),
severed from its
membrane anchor,
was cocrystallized
with Gs (green) to
give this crystal
structure. The plant
terpene forskolin
(yellow) is a drug
that strongly
stimulates the
enzyme, and GTP
(red) bound to Gs
triggers interaction
of Gs with adenylyl
cyclase.
Self-
inactivation of
Gs
The protein’s
intrinsic GTPase
activity, in many
cases stimulated by
RGS proteins
(regulators of G
protein signaling),
determines how
quickly bound GTP
is hydrolyzed to
GDP and thus how
long the G protein
remains active.
Activation of cAMP-dependent protein kinase, PKA
Desensitizati
on of the
adrenergic
receptor in
the
continued
presence of
epinephrine
This process
is mediated
by two
proteins:
beta-
adrenergic
protein
kinase (ARK)
and beta-
arrestin (arr;
arrestin 2).
Some Signals That Use cAMP as
Second Messenger
N Engl J Med Vol. 334 No. 9 580
 Principales receptores
adrenérgicos con sus
correspondientes sistemas de
transducción. Las proteínas
reguladoras G acopladas al
guanosintrifosfato (GTP) se
clasifican sobre la base de sus
efectos estimuladores (Gs) o
inhibidores (Gi) sobre la
actividad de la unidad
catalítica (C) de la
adenililciclasa. La proteína
Gq reguladora de la
fosfolipasa C (PLC) facilita la
hidrólisis del fosfatidilinositol
(PIP2) en diacilglicerol (DAG)
e inositoltrifosfato (IP3). La
proteín-cinasa A (PKA) y la
proteíncinasa C (PKC) son
enzimas efectoras cuya
actividad es generada o
inhibida por los sistemas de
segundo mensajero (AMPc,
PLC, Ca2+). AMPc:
adenosinmonofosfato cíclico;
GDP: guanosindifosfato.
Table 2. Preferred Linkages of Adrenergic Receptors to G-Protein
Families and Effectors.

THE NEW ENGLAND JOURNAL OF MEDICINE Feb. 29, 1996

Vol. 334 No. 9 580
 Recordar!
En general, los receptores beta suelen ser más sensibles que
los alfa, por lo que responden a dosis menores de fármaco.
A dosis ajas predominan acciones eta; a dosis ltas,
acciones lfa
Los receptores 2 y 2 son más sensibles a la adrenalina que
a la noradrenalina, estando más en contacto con las
catecolaminas circulantes.
Además, los receptores 2 y 2 tienen una localización
presináptica: 2 inhibe la liberación de noradrenalina y 2
facilita la liberación.
Hormone-activated
phospholipase C and IP3
Two intracellular second
messengers are produced in
the hormone-sensitive
phosphatidylinositol system:
inositol 1,4,5-trisphosphate
(IP3) and diacylglycerol. Both
contribute to the activation of
protein kinase C.
By raising cytosolic [Ca2], IP3
also activates other Ca2-
dependent enzymes; thus Ca2
also acts as a second
messenger.
 Phospholipase C cleaves PIP2 into diacylglycerol and inositol trisphosphate. R1
generally is stearate, and R2 is usually arachidonate. IP3 can be dephosphorylated (to
the inactive I-1,4-P2) or phosphorylated (to the potentially active I-1,3,4,5-P4).
Some Signals That Act through
Phospholipase C and IP3
Some Proteins Regulated
by Ca2 and Calmodulin
Common features of signaling systems that detect
hormones, light, smells, and tastes

 Serpentine receptors provide signal specificity, and their interaction with G proteins provides signal amplification. Heterotrimeric G
proteins activate effector enzymes: adenylyl cyclase (AC), phospholipase C (PLC), and phosphodiesterases (PDE) that degrade
cAMP or cGMP. Changes in concentration of the second messengers (cAMP, cGMP, IP3) result in alterations of enzymatic activities
by phosphorylation or alterations in the permeability (P) of surface membranes to Ca2, Na, and K. The resulting depolarization or
hyperpolarization of the sensory cell (the signal) is passed through relay neurons to sensory centers in the brain. In the beststudied
cases, desensitization includes phosphorylation of the receptor and binding of a protein (arrestin) that interrupts receptor–G
protein interactions. VR is the vasopressin receptor; other receptor and G protein abbreviations are as used in earlier illustrations.
Toxins produced by bacteria that cause cholera and
whooping cough (pertussis)

 These toxins are enzymes that catalyze transfer of the ADP-ribose moiety of NAD to an Arg
residue (cholera toxin) or a Cys residue (pertussis toxin) of G proteins: Gs in the case of cholera (as
shown here) and GI in whooping cough. The G proteins thus modified fail to respond to normal
hormonal stimuli. The pathology of both diseases results from defective regulation of adenylyl
cyclase and overproduction of cAMP.
 Receptores de Ach
Dos categorías: muscarínicos y nicotínicos.
Excitación de fibras preganglionares simpáticas y
parasimpáticas, y placa motriz: imitadas por la nicotina y
bloqueadas por la tubocurarina.
Excitación de fibras posganglionares parasimpáticas:
imitadas por la muscarina y bloqueadas selectivamente por
la atropina.
A los receptores responsables del primer tipo de respuestas
se los denominó nicotínicos y a los del segundo tipo,
muscarínicos.
The Acetylcholine Receptor
 Receptores nicotínicos

El receptor nicotínico pertenece a la familia de los

canales iónicos receptor-dependientes, de la que
también forman parte otros neurotransmisores como el
GABA, la glicina o el glutamato.
Son los encargados de mediar la rápida transmisión
sináptica tanto en el SNC como en el periférico (del
orden de 1-10 mseg).
 Receptores Nicotínicos

Los receptores nicotínicos forman parte de un canal iónico

cuya abertura controlan.
Receptores
muscarínicos
Los receptores
muscarínicos
participan de:
- transmisión
interneuronal en el
SNC
- ganglios vegetativos y
plexos nerviosos
- contracción del
músculo liso
- génesis y conducción
de estímulos cardíacos
- secreciones exocrina y
endocrina
 Receptores Muscarínicos

Los muscarínicos están asociados a diversos tipos de

proteínas G mediante las cuales activan sistemas efectores
de diversa naturaleza.
 Receptores muscarínicos
Cinco subtipos moleculares
Todos ellos asociados a proteínas G
Todos los subtipos de receptores muscarínicos se
encuentran en neuronas del SNC
En las neuronas ganglionares del sistema vegetativo:
receptores M1.
En los tejidos periféricos, los receptores M2
predominan en el corazón (nodos sinoauricular y
auriculoventricular, y músculo auricular) y, en mucho
menor grado, en otras células musculares lisas.
Los receptores M3 se encuentran principalmente en
células secretoras, musculares lisas y endotelio
Los M4 están presentes en las células endoteliales
vasculares, en neuronas ganglionares, vasos deferentes y
útero.
Receptores muscarínicos
Localización de receptores Muscarínicos
Localización de receptores Muscarínicos
Mecanismo de acción: receptores
corticoides
El complejo receptor-glucocorticoide en el citoplasma,
penetra en el núcleo e interactúa con secuencias
específicas de ADN localizadas en las zonas de
regulación de los genes, denominadas elementos de
respuesta a glucocorticoides (GRE) y son las que
dotan de especificidad a la inducción de la
transcripción genética.
El glucocorticoide modula la transcripción, modulación
que puede ser positiva si fomenta la síntesis de una
determinada proteína o negativa si la inhibe.
Muchas de las poderosas acciones de los
glucocorticoides, tanto fisiológicas como
farmacológicas, aparecen tras un período de latencia
de varias horas.
Intracellular mechanism of
action of the glucocorticoid
receptor
 The figure shows the molecular pathway by
which cortisol (labeled S) enters cells and
interacts with the glucocorticoid receptor
(GR) to change GR conformation (indicated
by the change in shape of the GR), induce
GR nuclear translocation, and activate
transcription of target genes. The example
shown is one in which glucocorticoids
activate expression of target genes; the
expression of certain genes, including pro-
opiomelanocortin (POMC) expression by
corticotropes, is inhibited by glucocorticoid
treatment. CBG, corticosteroid-binding
globulin; GR, glucocorticoid receptor; S,
steroid hormone; HSP90, the 90-kd heat-
shock protein; HSP70, the 70-kd heat-shock
protein; IP, the 56-kd immunophilin; GRE,
glucocorticoid-response elements in the
DNA that are bound by GR, thus providing
specificity to induction of gene transcription
by glucocorticoids. Within the gene are
introns (unshaded) and exons (shaded);
transcription and mRNA processing leads to
splicing and removal of introns and
assembly of exons into mRNA.
Existen dos tipos de receptores.
- Los receptores de tipo II, fijan exclusivamente a los
glucocorticoides (receptores glucocorticoides
propiamente dichos)
- Los receptores de tipo I, tienen igual afinidad por
los glucocorticoides y los mineralocorticoides.
- Los receptores de tipo II están: en las células de los
órganos diana de los glucocorticoides, y en el
cerebro, donde se localizan tanto en múltiples
neuronas como en las células de la glia. Son muy
abundantes en las neuronas implicadas en la
respuesta al estrés (núcleo paraventricular y sistema
límbico).
- Los receptores de tipo I se encuentran en:
determinadas neuronas límbicas (hipocampo y
septum) y en otras áreas cerebrales definidas (áreas
periventriculares y núcleo del tracto solitario).
Typical steroid hormone receptors

These receptor proteins have a binding site for the

hormone, a DNA-binding domain, and a region that
activates transcription of the regulated gene. The
highly conserved DNA-binding domain has two zinc
fingers.
 Genomic
Location and
Organization
of the Human
Glucocorticoi
d Receptor
(GR)

N Engl J Med
2005;353:1711-23

 Diversity in the expression and function of the glucocorticoid receptor results from
alternative sites for the initiation of transcription (exon 1A, 1B, or 1C), as well as
alternative splicing of pre–messenger RNA (mRNA) at exon 9a or 9b. Additional
variation in the structure and function of the protein results from alternative sites for
the initiation of translation within exon 2 and post-translational modifications in the
form of phosphorylation (P), ubiquination (Ub), and sumoylation (Sumo). DBD
denotes DNA-binding domain, LBD ligand-binding domain, and hGR human GR.
Regulation of the Relaxation of Vascular Smooth Muscle by Nitric Oxide
Nitric oxide activates
soluble guanylyl
cyclase, leading to
the activation of
cyclic guanosine 3´,
5´-monophosphate
(cGMP)–dependent
protein kinase
(cGKI). In turn, cGKI
decreases the
sensitivity of myosin
to calcium-induced
contraction and
lowers the
intracellular calcium
concentration by
activating calcium-
sensitive potassium
channels and
inhibiting the
release of calcium
from the
sarcoplasmic
reticulum. cGMP is
degraded by
phosphodiesterase
type 5, which is
inhibited by
sildenafil and
zaprinast. GTP
denotes guanosine
triphosphate.

N Engl J Med 2005;353:2683-95.

Biochemical Fates of Inhaled Nitric Oxide at
the Alveolar-Capillary Membrane
 Small amounts of nitrogen
dioxide (NO2) may be
formed if inhaled nitric
oxide mixes with high
concentrations of oxygen
(O2) in the air space.
 Depending on the milieu of
the lung parenchyma, nitric
oxide may react with
reactive oxygen species
(derived from activated
leukocytes or ischemia-
reperfusion injury) to form
reactive nitrogen species
such as peroxynitrite.
 In the vascular space,
dissolved nitric oxide is
scavenged by
oxyhemoglobin (forming
methemoglobin and
nitrate) and to a lesser
extent, plasma proteins
(e.g., forming nitrosothiols,
which are stable
intravascular sources of
nitric oxide activity).

N Engl J Med 2005;353:2683-95.

Two types (isozymes) of guanylyl cyclase that participate in
signal transduction
 (a) One isozyme exists in
two similar membrane-
spanning forms that are
activated by their extracellular
ligands: atrial natriuretic
factor, ANF (receptors in cells
of the renal collecting ducts
and the smooth muscle of
blood vessels), and guanylin
(receptors in intestinal
epithelial cells). The guanylin
receptor is also the target of a
type of bacterial endotoxin that
triggers severe diarrhea.
 (b) The other isozyme is a
soluble enzyme that is
activated by intracellular
nitric oxide (NO); this form is
found in many tissues,
including smooth muscle of
the heart and blood vessels.
 Activation of the
insulin-receptor
Tyr kinase by
autophosphoryl
ation

 (a) In the inactive form of the Tyr kinase domain (PDB ID 1IRK), the activation loop
(blue) sits in the active site, and none of the critical Tyr residues (black and red ball-
and-stick structures) are phosphorylated. This conformation is stabilized by hydrogen
bonding between Tyr1162 and Asp1132. (b) When insulin binds to the chains of
insulin receptors, the Tyr kinase of each subunit of the dimer phosphorylates three
Tyr residues (Tyr1158, Tyr1162, and Tyr1163) on the other  subunit (shown here;
PDB ID 1IR3). (Phosphoryl groups are depicted here as an orange space-filling
phosphorus atom and red ball-and-stick oxygen atoms.) The effect of introducing
three highly charged P –Tyr residues is to force a 30 Å change in the position of the
activation loop, away from the substrate-binding site, which becomes available to bind
to and phosphorylate a target protein, shown here as a red arrow.
Schematic diagram of
the insulin receptor
heterodimer in the
activated state. IRS,
insulin receptor
substrate; tyr, tyrosine;
P, phosphate.
Pathways of insulin signaling
CHARACTERISTICS OF THE FIVE FACILITATED –
DIFFUSION GLUCOSE TRANSPORTERS

N Eng J Med
Volume 341
Number 4 248
Mechanisms Involved in the Translocation of GLUT-4 Glucose
Transporters in Muscle Cells and Adipocytes

N Eng J Med Volume 341 Number 4 248

Characteristics of Histamine Receptors
H1 H2 H3 H4
Size (amino acids) 487 359 373, 445, 365 390
G protein coupling Gq/11 (↑Ca2+; Gs (↑cAMP) Gi/o (↓cAMP) Gi/o (↓cAMP;
(second ↑cAMP) ↑Ca2+)
messengers)

Distribution Smooth muscle, Gastric parietal CNS: Cells of

endothelial cells, presynaptic, hematopoi
cells, CNS cardiac myenteric etic origin
muscle, plexus
mast cells,
CNS

Representative 2-CH3-histamine Dimaprit (R)-α-CH3- Clobenpropit

agonist histamine (partial?)
Representative Chlorpheniramine Ranitidine Thioperamide JNJ7777120
antagonist
Clobenpropit Thioperamide
Compounds affecting the H3 and H4 receptors exhibit some lack of specificity, although JNJ7777120 seems to be a relatively
specific H4 antagonist. JNJ7777120 is 1-[(5-chloro-1H-indol-2-yl) carbonyl]-4-methylpiperazine
The JAK-STAT transduction mechanism for the EPO receptor
Binding of erythropoietin
(EPO) causes dimerization
of the EPO receptor, which
allows the soluble Tyr
kinase JAK to bind to the
internal domain of the
receptor and
phosphorylate it on several
Tyr residues. The STAT
protein STAT5 contains an
SH2 domain and binds to
the P –Tyr residues on the
receptor, bringing the
receptor into proximity
with JAK. Phosphorylation
of STAT5 by JAK allows
two STAT molecules to
dimerize, each binding the
other’s P –Tyr residue.
Dimerization of STAT5
exposes a nuclear
localization sequence
(NLS) that targets STAT5
for transport into the
nucleus. In the nucleus,
STAT causes the expression
of genes controlled by
EPO. A second signaling
pathway is also triggered
by autophosphorylation of
JAK that is associated with
EPO binding to its
receptor. The adaptor
protein Grb2 binds P –Tyr
Oncogene-encoded defective EGF
receptor
The product of the
erbB oncogene (the
ErbB protein) is a
truncated version of
the normal receptor
for epidermal growth
factor (EGF). Its
intracellular domain
has the structure
normally induced by
EGF binding, but the
protein lacks the
extracellular binding
site for EGF.
Unregulated by EGF,
ErbB continuously
signals cell division.
 Initiation of signal transduction by receptors linked to Jak kinases. The receptors (R) that bind prolactin, growth
hormone, interferons, and cytokines lack endogenous tyrosine kinase. Upon ligand binding, these receptors
dimerize and an associated protein (Jak1, Jak2, or TYK) is phosphorylated. Jak-P, an active kinase,
phosphorylates the receptor on tyrosine residues. The STAT proteins associate with the phosphorylated receptor
and then are themselves phosphorylated by Jak-P. STATP dimerizes, translocates to the nucleus, binds to
specific DNA elements, and regulates transcription. The phosphotyrosine residues of the receptor also bind to
several SH2 domain-containing proteins. This results in activation of the MAP kinase pathway (through SHC or
GRB2), PLCγ, or PI-3 kinase.
  NF-κB consists of
two subunits, p50
Regulation of the NF-κB pathway and p65, which
regulate
transcription of
many genes when
in the nucleus. NF-
κB is restricted
from entering the
nucleus by IκB, an
inhibitor of NF-κB.
IκB binds to—and
masks—the
nuclear
localization signal
of NF-κB.
 This cytoplasmic
protein is
phosphorylated by
an IKK complex
which is activated
by cytokines,
reactive oxygen
species, and
mitogens.
Phosphorylated
IκB can be
ubiquitinylated
and degraded, thus
releasing its hold
on NF-κB.
Glucocorticoids
affect many steps
in this process
Arachidonic acid products
Simplified Two-State Model of the Histamine H
1-Receptor

 In Panel A, the inactive state of the histamine H 1-receptor is in equilibrium

with the active state. In Panel B, an agonist, which has a preferential affinity
for the active state, stabilizes the receptor in this conformation and
consequently causes a shift in the equilibrium toward the active state. In
Panel C, an inverse agonist, which has a preferential affinity for the inactive
state, stabilizes the receptor in this conformation and consequently causes a
shift in the equilibrium toward the inactive state. All known H 1-antihistamines
function as inverse agonists. Intracellular and extracellular are defined in
relation to the cell membrane. The purple serpentine line denotes the G-
protein–coupled receptor, and green the cell membrane.
 N Engl J Med 2004;351:2203-17.
Complejo
receptor
GABA-
benzodiazepi
na-ionóforo
Cl–
 Se muestran los
diferentes sitios
receptores dentro
del complejo y se
señalan algunos
ejemplos de los
ligandos que
interactúan con
ellos como
agonistas,
antagonistas y
agonistas
Gracias
 BIBLIOGRAFÍA

- Las Bases Farmacológicas de la Terapéutica - Goodman y

Gilman - 13ª Edición, 2019

- Farmacología Básica y Clínica – Velázquez - 19ª Edición,

2019 – Editorial Médica Panamericana.

- Farmacología Humana – Jesús Flórez – 6ta. Edición, 2014