What Are the Differences between Antagonist and Agonist Muscles?

Antagonist binding to the receptor does not cause a biological effect by itself, but blocks the agonist-mediated effect of the receptor. Antagonists can be divided into two categories based on whether they reversibly compete with agonists that bind to the receptor.

Chinese name: Antagonist
Foreign name: antagonist

Definition: A class of substances without intrinsic activity
Function: Can bind to receptors

Antagonist classification

From the perspective of distinguishing between competitive and non-competitive antagonists, the effects of competitive antagonists can be countered by increasing agonist concentrations, while the effects of non-competitive antagonists cannot be countered by increasing agonists; competitive antagonists can increase ED. ₅₀ values, while non-competitive antagonists cannot.

Competitive antagonist

The drug has an affinity for the receptor but does not produce a receptor agonistic effect, which can prevent the binding of the agonist to the receptor. When the agonist concentration is fixed, increasing the concentration of the reversible competitive antagonist can gradually inhibit the response produced by the agonist. At a high concentration, the antagonist can completely prevent the reaction from occurring. Conversely, a sufficiently high concentration of agonist can remove the effect of a certain concentration of antagonist and still achieve the maximum effect E _max . Because the antagonism is competitive, the presence of the antagonist makes it necessary to increase the concentration of the agonist to reach a specific response height, which causes the agonist concentration-response curve to shift to the right in parallel. Other antagonists have the ability to inhibit the receptor's intrinsic activity in addition to preventing the binding of the agonist to the receptor. From a therapeutic perspective, the significance of this competitive antagonism is: The degree of inhibition of a competitive antagonist depends on the concentration of the antagonist. It is meaningful to adjust the dosage according to the concentration of the drug entering the body to produce the desired therapeutic effect. The clinical response to an antagonist depends on the concentration of the agonist that binds to the receptor.

Antagonist non-competitive antagonist

A drug that binds to a receptor protein at a different site from the agonist binding site and prevents the agonist from causing the receptor to agonize. In the dose-response relationship graph, non-competitive antagonism usually reduces the slope and height of the response curve, and also causes a certain degree of right-shift of the response curve. Drugs capable of binding to receptor proteins that differ from agonist binding sites are often referred to as allosteric modulators. Constitutive modulators can change receptor function, but do not agonize the receptor. Benzodiazepines are a typical example ^[1] .

Antagonist Drugs

Mscopolamine Antagonist M receptor antagonist: scopolamine

The drug is a belladonna alkaloid, which has a stronger effect on the central nervous system and lasts longer than atropine. The central nervous system can be inhibited at the treatment dose, and it has obvious sedative effects, such as drowsiness, oblivion, fatigue, and rapid eye movement sleep phase shortening, but it also produces excitatory effects at high doses. In addition, there are euphoric effects, so it is easy to cause drug abuse. This drug is mainly used before anesthesia, not only can inhibit glandular secretion, but also CNS, so it is better than atropine. In addition, the crystal can block short-term memory, and this forgetfulness effect is often used in anesthesia. The drug can also be used to treat motion sickness. Its mechanism may be related to its inhibition of vestibular inner ear function or cerebral cortex function and gastrointestinal motility. It can be combined with diphenhydramine to increase the efficacy. For motion sickness, prophylactic administration is more effective than application after the onset of the condition. Commonly used for seasickness and motion sickness, and also for vomiting caused by pregnancy or radiation sickness. This medicine also has a central anticholinergic effect, and has a certain effect on Parkinson's disease, which can improve symptoms such as tremor, salivation and muscle rigidity. The peripheral effect is similar to that of atropine, with only a difference in the intensity of the action. Among them, the inhibition of glandular secretion is stronger than that of atropine, the pupil dilation and the regulation of paralysis are slightly weaker than that of atropine, and the effect on the cardiovascular system is weak. Adverse reactions and contraindications were similar to atropine.

Nsuccinylcholine Antagonist N receptor antagonist: succinylcholine

It is composed of succinic acid and two molecules of choline. It is easily destroyed in alkaline solutions. If mixed with thiopental sodium, the activity will quickly decrease.

[Pharmacokinetics] After entering the blood, this drug is quickly hydrolyzed by pseudocholinesterase in the blood and liver to produce succinic monocholine and choline. The former is hydrolyzed into choline and succinic acid by the same enzyme. The effect disappears. Succinylcholine also has muscle relaxant activity, but only 1/50 of succincholine. Due to rapid metabolism and uniform distribution in the body, only about 10% to 15% of the dose reaches the neuromuscular junction. About 2% are excreted in the kidney in the original form, and the rest are excreted in the form of degradation products with the urine. It can inhibit pseudocholinesterase, so it can strengthen and prolong the muscle relaxation effect of succincholine.

[Pharmacological action] The skeletal muscle relaxation is fast and short-lived and easy to control. After an intravenous injection of 10-30 mg, uncoordinated muscle bundle tremors were seen in 20 seconds. It became relaxed after 1 minute, peaked in 2 minutes, and the effect disappeared in 5 minutes. Muscle relaxation starts from the neck muscles and gradually spreads to the scapula, limbs and abdomen. The neck and limb muscles are the most obvious, followed by the face, tongue, throat and masticatory muscles, which have the weakest effect on the respiratory muscles, but on the throat and tracheal smooth muscle Strong effect.

[Clinical application] The skeletal muscle relaxation effect of this product is fast and transient. The intravenous administration is suitable for short-term operations such as endotracheal intubation, bronchoscopy and esophagoscopy. It can also be administered intravenously as an adjuvant to general anesthesia to reduce the amount of general anesthesia. Under shallow anesthesia, skeletal muscles are completely relaxed, and surgery can be performed smoothly for a long time. The drug can cause a strong sense of suffocation, so it is forbidden for sober patients. After intravenous anesthesia with thiopental sodium, succinylcholine is given. In addition, the drug can also be used in the treatment of electric shock. Due to the large individual differences of the drug, the speed of administration needs to be adjusted according to the effect to obtain a satisfactory effect.

Adverse reactions

(1) Asphyxia or apnea: Excessive amounts of this product can easily cause paralysis of the respiratory muscles. Genetic cholinesterase deficiency or abnormal enzymes can cause diaphragmatic paralysis and apnea. Therefore, an artificial respirator must be provided.

(2) Muscle bundle tremor: This product can cause transient muscle bundle tremor before muscle relaxation, which can damage muscle spindle and cause muscle soreness. It usually heals itself within 3-5 days.

(3) Increased blood potassium: When this product makes skeletal muscle cells depolarize for a long time, a large amount of K is released from the cells, resulting in an increase in blood potassium.

(4) Fever: When halothane is used as an anesthetic, the simultaneous application of succinylcholine can occasionally cause malignant hyperthermia in genetically susceptible people with autosomal abnormalities. Often the main cause of death from anesthesia. Once it occurs, urgent measures must be taken to quickly cool the patient, give oxygen, correct acidosis, antihistamine treatment, etc., and simultaneously give dantrolene, block the release of calcium from the sarcoplasmic reticulum of muscle cells, thereby reducing heat generation And relax the muscles.

(5) Elevated intraocular pressure: This medicine can cause temporary contraction of extraocular skeletal muscles and cause elevated intraocular pressure. Therefore, it is contraindicated in glaucoma and cataract lens removal.

(6) Others: This drug has the effect of increasing glandular secretion and promoting histamine release.

[Contraindications] This medicine can cause a strong sense of suffocation, so it is contraindicated in sober patients. The drug can be given after anesthesia with thiopental sodium. Because it is prone to cause high potassium, it should be used with caution in patients with high blood potassium such as burns, extensive soft tissue damage, hemiplegia, cerebrovascular accidents, malignant tumors and renal insufficiency. This product can make the extraocular muscles contract choroidal vasodilation, leading to increased intraocular pressure. It is prohibited in patients with glaucoma and cataract lens removal. Patients with hereditary cholinesterase deficiency, severe liver dysfunction, malnutrition, and electrolyte disorders should be used with caution.

[Drug interaction] This product can be decomposed in alkaline solution, so it should not be mixed with thiopental sodium. Any drug that can reduce the activity of pseudocholine ester can enhance its effect, such as cholinesterase inhibitors, cyclophosphamide, nitrogen mustard and other anti-tumor drugs, procaine and other local anesthetics. Some aminoglycoside antibiotics such as kanamycin and polymyxin B also have muscle relaxation effects. When used in combination with this product, it can easily cause respiratory paralysis, so it should be noted.

1prazosin Antagonist selective 1 receptor antagonist: prazosin prazosin

It is a synthetic product and selectively antagonizes ₁ receptor.

[Pharmacokinetics] The oral bioavailability is about 50% -70%, and the blood drug concentration reaches the peak in 1-3 hours. Plasma protein binding rate is high, only about 5% exists in free form. Most drugs are metabolized in the liver, and only 5% -11% are excreted through the kidney in their original form. t1 _{/ 2 is} about 2-3 hours, and the drug action time lasts 4-6 hours.

[Pharmacological effects] Blocking of the alpha ₁ receptors on arterioles and veins, dilate blood vessels, reduce peripheral resistance, and reduce blood circulation. It does not antagonize the ₂ receptor at the therapeutic dose, so it does not promote the release of NA. At the same time, it lowers blood pressure and has little effect on heart rate. In addition, it can relax the smooth muscle contraction of bladder neck, prostate sac and prostate urethra mediated by ₁ receptor, which can improve the difficulty of urination in benign prostatic hyperplasia. There are fewer ₁ receptors at the bottom of the bladder, so it has an effect on bladder contraction Smaller. Studies have shown that _1A receptors are mainly present in the prostate and may be the most important ₁ receptor subtype in controlling prostate smooth muscle.

[Clinical application] It is mainly used to treat patients with hypertension and benign prostatic hyperplasia, which can improve symptoms such as urethral obstruction and dysuria caused by benign prostatic hyperplasia. Because it can reduce the pre- and post-load of the heart, it can also be used to combat chronic heart dysfunction.

[Adverse reaction] The first medication can cause severe hypotension, syncope, palpitations, etc., which is called the "first dose effect", and it usually occurs 30-90 minutes after the first medication. More caution is needed for patients with liver and kidney dysfunction and elderly patients. Combined with diuretics or other antihypertensive drugs, the antihypertensive effect of this drug can be exacerbated. Other adverse reactions are dizziness, drowsiness, headache, fatigue, etc. The above symptoms can be reduced by reducing or continuing medication.

Antagonist Non-selective beta receptor antagonist: propranolol

Propranolol is a racemic product of the same amount of L- and D-isomers, and only L-isomers have an antagonistic effect on receptors. It has high fat solubility, more than 90% is absorbed orally, but the first pass elimination rate is 60% -70%, and the bioavailability is low, only about 30%. The amount of drugs reaching the systemic circulation varies widely, with blood drug concentrations up to 25 times. Propranolol easily crosses the blood-brain barrier. The plasma protein binding rate is high, about 93%. Mainly metabolized by the liver, the metabolite 4-hydroxypropranolol still has beta receptor antagonism. Plasma t _{1/2 is} about 2-5 hours. Clinical medication needs to start from a small dose and gradually increase to an appropriate dose. Propranolol has a strong antagonistic effect on receptors, but has low selectivity for ₁ and ₂ receptors. It has no intrinsic sympathetic activity and has membrane stabilization. It is mainly used in the treatment of arrhythmia, angina pectoris, hypertension, hyperthyroidism, etc. It can also treat anxiety, tremor, upper gastrointestinal bleeding caused by cirrhosis and prevent migraine.