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AHFS/Drugs.com | Monograph |
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Routes of administration | Parenteral |
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Pharmacokinetic data | |
Bioavailability | N/A |
Metabolism | Hydrolysis by plasma esterases |
Elimination half-life | 40–84 seconds |
Excretion | Renal |
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ECHA InfoCard | 100.000.388 |
Chemical and physical data | |
Formula | C13H20N2O2 |
Molar mass | 236.315 g·mol−1 |
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Procaine is a local anesthetic drug of the amino ester group. It is most commonly used in dental procedures to numb the area around a tooth [1] and is also used to reduce the pain of intramuscular injection of penicillin. Owing to the ubiquity of the trade name Novocain or Novocaine, in some regions, procaine is referred to generically as novocaine. It acts mainly as a sodium channel blocker. [2] Today, it is used therapeutically in some countries due to its sympatholytic, anti-inflammatory, perfusion-enhancing, and mood-enhancing effects. [3]
Procaine was first synthesized in 1905, [4] shortly after amylocaine. [5] It was created by the chemist Alfred Einhorn who gave the chemical the trade name Novocaine, from the Latin nov- (meaning "new") and -caine, a common ending for alkaloids used as anesthetics. It was introduced into medical use by surgeon Heinrich Braun.
Prior to the discovery of amylocaine and procaine, cocaine was a commonly used local anesthetic. [6] Einhorn wished his new discovery to be used for amputations, but for this surgeons preferred general anesthesia. Dentists, however, found it very useful. [7]
The primary use for procaine is as an anaesthetic.
Aside from its use as a dental anesthetic, procaine is used less frequently today, since more effective (and hypoallergenic) alternatives such as lidocaine (Xylocaine) exist. Like other local anesthetics (such as mepivacaine, and prilocaine), procaine is a vasodilator, thus is often coadministered with epinephrine for the purpose of vasoconstriction. Vasoconstriction helps to reduce bleeding, increases the duration and quality of anesthesia, prevents the drug from reaching systemic circulation in large amounts, and overall reduces the amount of anesthetic required. [8] As a dental anesthesic, for example, more novocaine is needed for root canal treatment than for a simple filling. [1] Unlike cocaine, a vasoconstrictor, procaine does not have the euphoric and addictive qualities that put it at risk for abuse.
Procaine, an ester anesthetic, is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-amino benzoic acid (PABA), which is then excreted by the kidneys into the urine.
A 1% procaine injection has been recommended for the treatment of extravasation complications associated with venipuncture, steroids, and antibiotics. It has likewise been recommended for treatment of inadvertent intra-arterial injections (10 ml of 1% procaine), as it helps relieve pain and vascular spasm.
Procaine is an occasional additive in illicit street drugs, such as cocaine. MDMA manufacturers also use procaine as an additive at ratios ranging from 1:1 up to 10% MDMA with 90% procaine, which can be life-threatening. [9]
Application of procaine leads to the depression of neuronal activity. The depression causes the nervous system to become hypersensitive, producing restlessness and shaking, leading to minor to severe convulsions.[ citation needed ] Studies on animals have shown the use of procaine led to the increase of dopamine and serotonin levels in the brain. [10] Other issues may occur because of varying individual tolerance to procaine dosage. Nervousness and dizziness can arise from the excitation of the central nervous system, which may lead to respiratory failure if overdosed. Procaine may also induce weakening of the myocardium leading to cardiac arrest. [11]
Procaine can also cause allergic reactions causing individuals to have problems with breathing, rashes, and swelling. Allergic reactions to procaine are usually not in response to procaine itself, but to its metabolite PABA. Allergic reactions are in fact quite rare, estimated to have an incidence of 1 per 500,000 injections. About one in 3000 white North Americans is homozygous (i.e. has two copies of the abnormal gene) for the most common atypical form of the enzyme pseudocholinesterase, [12] [13] and do not hydrolyze ester anesthetics such as procaine. This results in a prolonged period of high levels of the anesthetic in the blood and increased toxicity.
However, certain populations in the world such as the Vysya community in India commonly have a deficiency of this enzyme. [13]
Procaine can be synthesized in two ways.
Local anesthesia is any technique to induce the absence of sensation in a specific part of the body, generally for the aim of inducing local analgesia, i.e. local insensitivity to pain, although other local senses may be affected as well. It allows patients to undergo surgical and dental procedures with reduced pain and distress. In many situations, such as cesarean section, it is safer and therefore superior to general anesthesia.
A local anesthetic (LA) is a medication that causes absence of all sensation in a specific body part without loss of consciousness, providing local anesthesia, as opposed to a general anesthetic, which eliminates all sensation in the entire body and causes unconsciousness. Local anesthetics are most commonly used to eliminate pain during or after surgery. When it is used on specific nerve pathways, paralysis also can be induced.
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia and ventricular fibrillation. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding.
4-Aminobenzoic acid (also known as para-aminobenzoic acid or PABA because the two functional groups are attached to the benzene ring across from one another in the para position) is an organic compound with the formula H2NC6H4CO2H. PABA is a white solid, although commercial samples can appear gray. It is slightly soluble in water. It consists of a benzene ring substituted with amino and carboxyl groups. The compound occurs extensively in the natural world.
Benzocaine, sold under the brand name Orajel amongst others, is a local anesthetic, belonging to the amino ester drug class, commonly used as a topical painkiller or in cough drops. It is the active ingredient in many over-the-counter anesthetic ointments such as products for oral ulcers. It is combined with antipyrine to form A/B ear drops. In the US, products containing benzocaine for oral application are contraindicated in children younger than two years old. In the European Union, the contraindication applies to children under 12 years of age.
An anesthetic or anaesthetic is a drug used to induce anesthesia — in other words, to result in a temporary loss of sensation or awareness. They may be divided into two broad classes: general anesthetics, which result in a reversible loss of consciousness, and local anesthetics, which cause a reversible loss of sensation for a limited region of the body without necessarily affecting consciousness.
Pseudocholinesterase deficiency is an autosomal recessive inherited blood plasma enzyme abnormality in which the body's production of butyrylcholinesterase is impaired. People who have this abnormality may be sensitive to certain anesthetic drugs, including the muscle relaxants succinylcholine and mivacurium as well as other ester local anesthetics.
Infiltration analgesia is deposition of an analgesic (pain-relieving) drug close to the apex of a tooth so that it can diffuse to reach the nerve entering the apical foramina. It is the most routinely used in dental local treatment.
Benzonatate, sold under the brand name Tessalon among others, is a medication that is used for the symptomatic relief of cough. A 2023 systematic review found that there is inadequate evidence to support the effectiveness and safety of benzonatate for cough and highlighted rising safety concerns. Benzonatate is taken by mouth. Effects generally begin within 20 minutes and last 3 to 8 hours.
Bupivacaine, marketed under the brand name Marcaine among others, is a medication used to decrease sensation in a specific small area. In nerve blocks, it is injected around a nerve that supplies the area, or into the spinal canal's epidural space. It is available mixed with a small amount of epinephrine to increase the duration of its action. It typically begins working within 15 minutes and lasts for 2 to 8 hours.
Phentolamine, sold under the brand name Regitine among others, is a reversible nonselective α-adrenergic antagonist.
Methohexital or methohexitone is a drug which is a barbiturate derivative. It is classified as short-acting, and has a rapid onset of action. It is similar in its effects to sodium thiopental, a drug with which it competed in the market for anesthetics.
Chloroprocaine is a local anesthetic given by injection during surgical procedures and labor and delivery. Chloroprocaine vasodilates; this is in contrast to cocaine which vasoconstricts. Chloroprocaine is an ester anesthetic.
Alfred Einhorn was a German chemist most notable for first synthesizing procaine in 1905 which he patented under the name Novocain. Until that time the primary anesthetic in use was cocaine, however its undesirable side effects led scientists to seek out newer anesthetic drugs. Novocain was found to be comparatively safe and effective, although its anesthetic effects were weaker than cocaine and some patients proved highly allergic. However, none of the other anesthetics developed during this period proved more effective and Novocain quickly became the standard local anesthesia. Although its use has largely been replaced by lidocaine, it is still in use today, most frequently in dentistry.
Butyrylcholinesterase, also known asBChE, BuChE, BuChase, pseudocholinesterase, or plasma (cholin)esterase, is a nonspecific cholinesterase enzyme that hydrolyses many different choline-based esters. In humans, it is made in the liver, found mainly in blood plasma, and encoded by the BCHE gene.
Dental anesthesia is the application of anesthesia to dentistry. It includes local anesthetics, sedation, and general anesthesia.
Amino esters are a class of local anesthetics. They are named for their ester bond and are unlike amide local anaesthetics.
Dimethocaine, also known as DMC or larocaine, is a compound with a stimulatory effect. This effect resembles that of cocaine, although dimethocaine appears to be less potent. Just like cocaine, dimethocaine is addictive due to its stimulation of the reward pathway in the brain. However, dimethocaine is a legal cocaine replacement in some countries and is even listed by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) under the category “synthetic cocaine derivatives”. The structure of dimethocaine, being a 4-aminobenzoic acid ester, resembles that of procaine. It is found as a white powder at room temperature.
Nitrobenzoic acids are derivatives of benzoic acid. Two are commercially important. They are about ten times more acidic than the parent benzoic acid.
Adapted from Introduction to Organic Laboratory Techniques: A Microscale Approach, Pavia, Lampman, Kriz & Engel, 1989.