プロカイン

Pharmaceuticals

Pharmaceuticals -> Listed in ZINC15

log Kow= 1.92

1.8

2.1

Crystals, mp 153-156 °C, sol in water, alcohol /Nitrate/

Crystals. Six-sided plates, monoclinic or triclinic, mp 153-156 °C. One gram dissolves in 1 ml water and in 30 ml alcohol. Slightly sol in chloroform. Almost insoluble in ether. The pH of a 0.1 M aqueous solution is 6.0. /Hydrochloride/

ODORLESS; AQ SOLN ACID TO LITMUS; PKA 8.7; SMALL WHITE CRYSTALS; 1 G SOL IN 1 ML WATER OR 15 ML ALC; SLIGHTLY SOL IN CHLOROFORM; PRACTICALLY INSOL IN ETHER /HYDROCHLORIDE/

Sol in alcohol, ether, benzene, chloroform

Soluble in ethanol, ethyl ether, and benzene

61 °C

Slightly bitter taste; mp: 51 °C; needles from aq alcohol /Dihydrate/

61 °C

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Allergic contact dermatitis reported in doctors, dentists, and veterinarians; [Kanerva, p. 1829] Procaine allergy used to be a common skin sensitizer for dentists. There exists cross-reactivity between procaine, benzocaine, and tetracaine but not with lidocaine and other amide-type local anesthetics currently used. [Kanerva, p. 434]

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

WELL-KNOWN CLASS OF PROLONGING AGENTS...SKF-525-A...INHIBITS...MICROSOMAL ESTERASE ACTIVITY TOWARDS PROCAINE.

... /PROCAINE/ IS HYDROLYZED IN VIVO TO PRODUCE PARAAMINOBENZOIC ACID, WHICH INHIBITS THE ACTION OF SULFONAMIDES. THUS, LARGE DOSES SHOULD NOT BE ADMINISTERED TO PATIENTS TAKING SULFONAMIDE DRUGS.

PROCAINE IM CAN POTENTIATE PENTOBARBITAL ANESTHESIA... SYMPATHOMIMETICS...& MONOAMINE OXIDASE INHIBITORS MAY HAVE THEIR HYPERTENSIVE EFFECTS POTENTIATED BY PROCAINE. ...MAY POTENTIATE OR BE POTENTIATED BY PHENOTHIAZINE TRANQUILIZERS, CHOLINESTERASE INHIBITORS...& MUSCLE RELAXANTS SUCH AS SUCCINYLCHOLINE.

SUBSTRATE COMPETITION PROBABLY ACCOUNTS FOR INHIBITION OF SUCCINYLCHOLINE HYDROLYSIS BY PROCAINE.

For more Interactions (Complete) data for PROCAINE (17 total), please visit the HSDB record page.

Skin Sensitizer - An agent that can induce an allergic reaction in the skin.

The adverse effects of procaine administration are similar to those of other aminoester anesthetics. Increased intravascular levels mediate most side effects; this can be due to overdosage, entry into intravascular spaces, and potentiation from reduced metabolism. More rarely, patients may experience adverse effects secondary to hypersensitivity or idiosyncrasy.

Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.

An allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives); chest pain or slow or irregular heartbeats; dizziness or drowsiness; anxiety or restlessness; nausea or vomiting; trembling, shaking, or seizures (convulsions). Other less serious side effects such as numbness, tingling, or minor pain at or around the injection site are more likely to occur.(L1459)

IN 2...INSTANCES LOSS OF VISION FOLLOWED INJECTION OF PROCAINE FOR EXTRACTION OF TEETH. IN ONE OF THESE INSTANCES SEVERE VISUAL LOSS WAS NOTED WITHIN DAY FOLLOWING EXTRACTION & THERE WAS NO SUBSEQUENT IMPROVEMENT. ULTIMATELY OPTIC NERVES BECAME ATROPHIC & VISION WAS /SRP: REDUCED TO/ PERCEPTION OF HAND MOVEMENT.

RAPID IV ADMIN OR OVERDOSAGE CAN CAUSE CONVULSIONS, HYPOTENSION, RESPIRATORY FAILURE, & EVEN DEATH. ... HYPERSENSITIVITY REACTIONS ARE POSSIBLE.

FOLLOWING ABSORPTION FROM PARENTERAL ROUTES, PROCAINE IS A CENTRAL NERVOUS STIMULANT, PRODUCING RESTLESSNESS & TREMORS PROCEEDING TO CLONIC CONVULSIONS. STIMULATION IS FOLLOWED BY DEPRESSION, & DEATH IS USUALLY DUE TO RESPIRATORY FAILURE. ... ON RARE OCCASIONS SMALL DOSES HAVE PRODUCED CARDIOVASCULAR COLLAPSE & DEATH.

LD50 Rat sc 600 mg/kg

LD50 Mouse oral 350 mg/kg

LD50 Mouse ip 124 mg/kg

LD50 Mouse sc 300 mg/kg

LD50 Mouse iv 45 mg/kg

Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).

N01BA02

C - Cardiovascular system

S - Sensory organs

N - Nervous system

QC - Cardiovascular system

QS - Sensory organs

Procaine is an anesthetic agent indicated for production of local or regional anesthesia, particularly for oral surgery. Procaine (like cocaine) has the advantage of constricting blood vessels which reduces bleeding, unlike other local anesthetics like lidocaine. Procaine is an ester anesthetic. It is metabolized in the plasma by the enzyme pseudocholinesterase through hydrolysis into para-aminobenzoic acid (PABA), which is then excreted by the kidneys into the urine.

Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. When the influx of sodium is interrupted, an action potential cannot arise and signal conduction is thus inhibited. The receptor site is thought to be located at the cytoplasmic (inner) portion of the sodium channel. Procaine has also been shown to bind or antagonize the function of N-methyl-D-aspartate (NMDA) receptors as well as nicotinic acetylcholine receptors and the serotonin receptor-ion channel complex.

LOCAL ANESTHETICS BLOCK CONDUCTION BY DECREASING OR PREVENTING THE LARGE TRANSIENT INCREASE IN THE PERMEABILITY OF EXCITABLE MEMBRANES TO SODIUM IONS THAT NORMALLY IS PRODUCED BY A SLIGHT DEPOLARIZATION OF THE MEMBRANE. /LOCAL ANESTHETIC/

LOCAL ANESTHETICS BLOCK CONDUCTION IN NERVE PERHAPS BY COMPETING WITH CALCIUM @ SOME SITE THAT CONTROLS PERMEABILITY OF MEMBRANE. ... LOCAL ANESTHETICS ALSO REDUCE PERMEABILITY OF RESTING NERVE TO POTASSIUM AS WELL AS TO SODIUM IONS. /LOCAL ANESTHETICS/

AS THE ANESTHETIC ACTION PROGRESSIVELY DEVELOPS IN A NERVE, THE THRESHOLD FOR ELECTRICAL EXCITABILITY GRADUALLY INCREASES, THE RATE OF RISE OF THE ACTION POTENTIAL DECLINES, IMPULSE CONDUCTION SLOWS, & THE SAFETY FACTOR FOR CONDUCTION DECREASES; THESE FACTORS DECREASE THE PROBABILITY OF PROPAGATION OF THE ACTION POTENTIAL, AND NERVE CONDUCTION FAILS. /LOCAL ANESTHETICS/

POSTSYNAPTIC ACTION ... END-PLATE CURRENT IS MUCH PROLONGED BY PROCAINE. SIMILARLY, WHEN ... ADDED TO FLUID PERFUSING GANGLION, PREGANGLIONIC STIMULATION FAILS TO ELICIT POSTGANGLIONIC DISCHARGES & GANGLION CELLS BECOME INSENSITIVE TO STIMULATION BY ACETYLCHOLINE.

IN ADDITION TO BLOCKING CONDITIONS IN NERVE AXONS IN THE PERIPHERAL NERVOUS SYSTEM, LOCAL ANESTHETICS INTERFERE WITH THE FUNCTION OF ALL ORGANS IN WHICH CONDUCTION OR TRANSMISSION OF IMPULSES OCCURS. ... EFFECTS ON ... CNS, THE AUTONOMIC GANGLIA, THE NEUROMUSCULAR JUNCTION, & ALL FORMS OF MUSCLE. /LOCAL ANESTHETICS/

7.7 minutes

SERUM T/2 VALUES FOR PROCAINE WERE LONGER FOR PT WITH LIVER DISEASE (2.3 MIN), PT WITH RENAL FAILURE (1.4 MIN), & NEW-BORN INFANTS (1.4 MIN) THAN FOR HEALTHY ADULTS (0.66 MIN).

INFUSION OF 2% PROCAINE-HCL ADMIN TO 12 WOMEN UNDERGOING HYSTERECTOMY. STEADY-STATE PLASMA LEVELS WERE ACHIEVED WITHIN 20-30 MIN AFTER COMMENCEMENT OF INFUSION. AFTER TERMINATION OF INFUSION DISTRIBUTION T/2 OF 2.49 MIN & ELIMINATION T/2 OF 7.69 MIN.

Hydrolysis by plasma esterases to PABA

REDUCED RATE OF PROCAINE HYDROLYSIS IN SERUM FROM UREMIC PT IS DUE TO DECR ENZYME ACTIVITY RATHER THAN COMPETITIVE INHIBITION OF ENDOGENOUS SUBSTANCE IN SERUM.

... /Procaine/ is hydrolyzed in vivo to produce paraaminobenzoic acid ...

YIELDS 2-DIETHYLAMINOETHYL P-ACETAMIDOBENZOATE IN GUINEA PIG; BILLIAR, RB, & EIK-NES, KB, ARCHS BIOCHEM BIOPHYS, 115, 318 (1966). /FROM TABLE/

Hydrolysis by plasma esterases to PABA Route of Elimination: With normal kidney function, the drug is excreted rapidly by tubular excretion. Half Life: 7.7 minutes

Drugs that block nerve conduction when applied locally to nerve tissue in appropriate concentrations. They act on any part of the nervous system and on every type of nerve fiber. In contact with a nerve trunk, these anesthetics can cause both sensory and motor paralysis in the innervated area. Their action is completely reversible. (From Gilman AG, et. al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed) Nearly all local anesthetics act by reducing the tendency of voltage-dependent sodium channels to activate.

With normal kidney function, the drug is excreted rapidly by tubular excretion.

/PARA-AMINOBENZOIC ACID/ ... IS EXCRETED IN URINE TO EXTENT OF ABOUT 80%, EITHER UNCHANGED OR IN CONJUGATED FORM. ONLY 30% OF DIETHYLAMINOETHANOL CAN BE RECOVERED IN URINE; REMAINDER UNDERGOES METABOLIC DEGRADATION.

... IT HAS BEEN SHOWN THAT, FOLLOWING INTRODUCTION OF PROCAINE INTO EPIDURAL SPACE IN USUAL ANESTHETIC DOSE, SIGNIFICANT CONCN IS ACHIEVED IN SPINAL FLUID.

RATE OF ENZYMATIC HYDROLYSIS OF LOCAL ANESTHETIC AGENTS BY SPINAL FLUID IS SLOW. ... DURATION OF ANESTHESIA DEPENDS UPON RATE AT WHICH DRUG IS REMOVED FROM CSF & FROM NERVE ROOTS WHERE IT EXERTS ITS ACTION. /LOCAL ANESTHETICS/

ABSORPTION DOES NOT TAKE PLACE FROM STOMACH, ESOPHAGUS, OR BLADDER IF MUCOSA INTACT. /LOCAL ANESTHETICS/

For more Absorption, Distribution and Excretion (Complete) data for PROCAINE (7 total), please visit the HSDB record page.

Used as a local anesthetic; [Kanerva, p. 1829]

MEDICATION

Use (kg; approx.) in Germany (2009): >750

It is used primarily to reduce the pain of intramuscular injection of penicillin, and it is also used in dentistry. [Wikipedia]

USUALLY PREPD BY INTERACTION OF 2-DIETHYLAMINOETHANOL WITH P-NITROBENZOYL CHLORIDE, FOLLOWED BY REDUCTION OF 2-DIETHYLAMINOETHYL P-NITROBENZOATE, OR BY ESTERIFYING P-AMINOBENZOIC ACID WITH 2-DIETHYLAMINOETHANOL USING H2SO4 AS CATALYST: US PATENT 812,554 (1906).

Prepn: A. Einhorn, U.S pat 812,554 (1906); Idem, Ann. 371, 125 (1909); A. Einhorn, E. Uhlfelder, ibid. 131.

(1) By heating chloroethyl-p-nitrobenzoic ester with diethylamine for 24 hours under pressure at 120 °C. The product is then reduced with tin and hydrochloric acid. (2) By condensation of ethylene chlorohydrin with diethylamine. The chloroethyldiethylamine formed is heated with sodium-p-aminobenzoate. /Hydrochloride/

Prepared by reacting benzocaine and 2-diethylaminoethanol in the presence of catalytic amounts of sodium and simultaneous removal of the nascent ethanol by distillation. /Hydrochloride/

IT IS AVAIL AS OFFICIAL INJECTION. MARKET PREPN INCL FOLLOWING: AMPULS OR VIALS OF 0.5, 1, 2, OR 10% SOLN WITHOUT EPINEPHRINE, OR 1 OR 2% SOLN WITH EPINEPHRINE IN CONCN OF 1:50,000-1:100,000, FOR INFILTRATION & NERVE BLOCK; 5-20% SOLN IN AMPULS, FOR SPINAL ANESTHESIA ... /HYDROCHLORIDE/

... AMPULS OF STERILE PROCAINE HYDROCHLORIDE CRYSTALS (50-500 MG), FOR SPINAL ANESTHESIA; 0.1 OR 0.2% PROCAINE HYDROCHLORIDE IN ISOTONIC SODIUM CHLORIDE SOLN, FOR IV INFUSION. /HYDROCHLORIDE/

Grade: USP /Hydrochloride/

INCOMPATIBILITIES: ALKALOIDAL PRECIPITANTS...INCL SOLN OF IODINE & MERCURIC CHLORIDE, CAUSE PRECIPITATION & ALKALIES LIBERATE INSOL PROCAINE BASE. /HYDROCHLORIDE/

Particularly useful with silver nitrate because no percipitate forms /nitrate/

AS A GENERAL RULE, SMALL NERVE FIBERS ARE MORE SUSCEPTIBLE TO THE ACTION OF LOCAL ANESTHETICS THAN ARE LARGE FIBERS. ... SENSATION OF PAIN USUALLY IS THE FIRST MODALITY TO DISAPPEAR ... /LOCAL ANESTHETICS/