Mechanisms of influence on synaptic transmission
Pharmacological agents are capable of interfering with synapse function at several levels. The following mechanisms of their influence are distinguished:
- Stimulation of neurotransmitter release. This is how sympathomimetics work (e.g., ephedrine, amphetamine, and tyramine found in food products). They displace noradrenaline molecules from presynaptic terminals directly into the synaptic cleft.
- Direct action on receptors. Substances act as adrenomimetics (direct stimulating action) or adrenoblockers (antagonists). It is these groups that have found the widest application in medicine.
- Inhibition of reuptake. Cocaine and tricyclic antidepressants (amitriptyline, imipramine) block the transport systems of the presynaptic membrane. Noradrenaline accumulates in the cleft, and its effect is repeatedly amplified.
- Inhibition of neurotransmitter degradation. MAO inhibitors (e.g., non-selective nialamide) block the monoamine oxidase enzyme in the cytoplasm, preventing the breakdown of free noradrenaline.
- Disruption of storage (depletion). Sympatholytics (reserpine) block the transport systems of vesicle membranes. Noradrenaline cannot enter the vesicles, which leads to the depletion of neurotransmitter stores.
Types and localization of adrenoreceptors
Receptors are divided into two main types — $\alpha$ (subtypes $\alpha_1$, $\alpha_2$) and $\beta$ (subtypes $\beta_1$, $\beta_2$, $\beta_3$). Their functions and sensitivity depend on their location relative to the synapse:
- Postsynaptic (predominantly $\alpha_1$, $\beta_1$). Located on the membrane of target cells (effector cells). They are excited by noradrenaline released from nerve endings during classical synaptic transmission.
- Extrasynaptic (predominantly $\alpha_2$, $\beta_2$). Located on cells that lack direct sympathetic innervation. They respond to circulating adrenaline in the blood (hormone of the adrenal medulla), while $\alpha_2$ receptors also respond to circulating noradrenaline.
- Presynaptic (predominantly $\alpha_2$). Located on the nerve endings themselves and regulate synapse function via negative feedback: their stimulation inhibits further release of noradrenaline from varicosities.
Physiological effects of receptor stimulation
Each receptor subtype triggers specific reactions in target organs.
Effects of $\alpha$-adrenoreceptors:
- $\alpha_1$ receptors: cause contraction of vascular smooth muscle (vasoconstriction) and contraction of the radial muscle of the iris (pupil dilation — mydriasis). They are also localized in the sphincters of the gastrointestinal tract, the urinary bladder, and the spleen capsule.
- $\alpha_2$ receptors: constrict blood vessels, and at the presynaptic level, they reduce noradrenaline release.
Effects of $\beta$-adrenoreceptors:
- $\beta_1$ receptors: stimulate the heart, increasing the force of contractions (inotropy), heart rate (chronotropy), and conductivity (dromotropy). This sharply increases the myocardial oxygen demand. In the kidneys, they activate renin secretion.
- $\beta_2$ receptors: are responsible for relaxation. They reduce vascular tone (vasodilation), dilate bronchi, and relax the uterine myometrium. In metabolism, they trigger glycogen breakdown (glycogenolysis).
Classification of stimulating agents
All drugs that stimulate adrenergic synapses can be divided into two subgroups according to their mechanism of action:
- Adrenomimetics (direct-acting). Independently bind to receptors and activate them, mimicking the effect of noradrenaline. Depending on selectivity, they are divided into $\alpha$-adrenomimetics, $\beta$-adrenomimetics, and mixed $\alpha,\beta$-adrenomimetics.
- Sympathomimetics (indirect-acting). Do not directly interact with receptors. Their task is to increase the release or accumulation of their own neurotransmitter in the synaptic cleft. The accumulated noradrenaline then secondarily excites the receptors itself.
Briefly: answers to topical questions
What is the classification of adrenoblockers?
The classification of adrenoblockers is based on their preferential affinity for a specific type of receptor. There are three main groups of drugs:
- $\alpha$-adrenoblockers — block alpha receptors. According to selectivity of action, they are divided into non-selective ($\alpha_1, \alpha_2$) and selective ($\alpha_1$).
- $\beta$-adrenoblockers — block beta receptors. They are subdivided into non-selective (blocking $\beta_1$ and $\beta_2$) and selective $\beta_1$ blockers.
- $\alpha, \beta$-adrenoblockers — mixed-action drugs that block both types of receptors.
Which drugs belong to beta-2 adrenomimetics?
The group of beta-2 adrenomimetics includes drugs that are divided by duration of action into short-acting and long-acting. The following representatives are mentioned in sources:
- Fenoterol — a short-acting drug for relieving acute bronchospasm.
- Salbutamol — a short-acting drug ("rescue medication") for acute bronchospasm attacks.
- Formoterol — a long-acting drug used for maintenance therapy.
- Hexoprenaline — a selective drug used primarily in obstetrics.
What are the indications for prescribing alpha-adrenomimetics?
Indications/purposes of using alpha-adrenomimetics in the sources can be illustrated by the example of phenylephrine (mesaton):
- In cardiovascular failure — administration of mesaton as a sympathomimetic is possible.
- Topical use in eye drops — causes pupil dilation (mydriasis) due to contraction of the radial muscle of the iris.
The pharmacodynamic basis of these effects: stimulation of postsynaptic vascular $\alpha_1$-adrenoreceptors causes vasoconstriction and an increase in blood pressure.
Which enzymes break down noradrenaline?
The destruction and inactivation of noradrenaline in the synapse are carried out by two main enzymes:
- Monoamine oxidase (MAO, including the mitochondrial enzyme MAO-A) — is responsible for the enzymatic breakdown of the free neurotransmitter inside presynaptic nerve terminals (in the cytoplasm).
- Catechol-O-methyltransferase (COMT) — is involved in the enzymatic breakdown of the remaining part of the neurotransmitter.
These enzymes metabolize the fraction of catecholamines that has not undergone neuronal reuptake.
The "organ rule" will help remember the localization of $\beta$ receptors: $\beta_1$ — we have one heart (stimulation of myocardial functions), $\beta_2$ — we have two lungs (bronchodilation).
Class and exam questions
What is the difference between adrenomimetics and sympathomimetics?
Adrenomimetics act directly on adrenoreceptors, replacing the natural neurotransmitter. Sympathomimetics do not touch the receptors, but cause the neuron to accumulate or release more of its own noradrenaline.
How do receptors regulate norepinephrine release?
The process is controlled by presynaptic receptors. Stimulation of alpha-2 receptors inhibits neurotransmitter release (negative feedback), while stimulation of beta receptors, conversely, increases it (positive feedback).
Why does diastolic pressure decrease upon beta-receptor stimulation?
Stimulation of beta-2 receptors in the smooth muscle of blood vessels leads to their relaxation. This reduces total peripheral vascular resistance, which causes a drop in diastolic pressure.
What else to study on this topic
- Mechanisms of action of sympatholytics and the process of neurotransmitter store depletion
- Pharmacodynamics of adrenoblockers and their use in cardiology
- Hemodynamic effects: how systolic and mean blood pressure change during synapse stimulation
- Mechanisms of neuronal reuptake and the effect of antidepressants on them
- Localization and functions of beta-3 adrenoreceptors
Master the entire topic in the «Pharmacology» course
This is a summary. The course covers everything tested in classes and exams.
- Complete study guide on "Drugs acting on adrenergic synapses" and 5,304 other pages on the subject
- Assignments and quizzes after every topic — just like in a colloquium
- AI tutor answers questions on the topic anytime
- 116 video lessons on the subject
Other topics in the section "Drugs Acting on Adrenergic Synapses"
Free video lessons: pharmacologyShort lessons with study notes — no registration required.
Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.