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Procaine (also known as Novocaine HCl), the HCl salt of the local anesthetic Procaine, is an inhibitor of sodium channel, NMDA receptor and nAChR with IC50 of 60 μM, 0.296 mM and 45.5 μM, which is also an inhibitor of 5-HT3 with KD of 1.7 μM. Procaine acts mainly by inhibiting sodium influx through voltage gated sodium channels in the neuronal cell membrane of peripheral nerves. 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.
Physicochemical Properties
| Molecular Formula | C₁₃H₂₀N₂O₂ |
| Molecular Weight | 236.31 |
| Exact Mass | 236.152 |
| CAS # | 59-46-1 |
| Related CAS # | Procaine hydrochloride;51-05-8 |
| PubChem CID | 4914 |
| Appearance | White to off-white solid powder |
| Density | 1.1±0.1 g/cm3 |
| Boiling Point | 373.6±22.0 °C at 760 mmHg |
| Melting Point | 61ºC |
| Flash Point | 179.8±22.3 °C |
| Vapour Pressure | 0.0±0.8 mmHg at 25°C |
| Index of Refraction | 1.543 |
| LogP | 2.36 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 7 |
| Heavy Atom Count | 17 |
| Complexity | 222 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | MFDFERRIHVXMIY-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C13H20N2O2/c1-3-15(4-2)9-10-17-13(16)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3 |
| Chemical Name | 2-(diethylamino)ethyl 4-aminobenzoate |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| ln Vitro | In whole-cell patch clamp recordings, 5-HT3 clamp-conducted inward currents are inhibited by procaine (0.01-100 μM). With a KD of 1.7 μM, procaine seems to produce complementary inhibition of 5-HT3 [1]. Procaine is a DNA methylator that uses capillary fast or high-efficiency enzymatic digestion of whole DNA to reduce the amount of 5-methylcytosine DNA by 40%. Moreover, heavily methylated CpG islands can be demethylated by procaine. These almonds are likewise subject to a growth-inhibitory action by propacine, which results in mitotic Manhattan splitting [2]. Procaine alters the synaptic transmission of a portion of the amygdala's output and excites cells in the limbic system [3]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion 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. Metabolism / Metabolites 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 Biological Half-Life 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. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation The term "Novocaine" (procaine) is often equated to local anesthetic. The exact identity of any local anesthetic should be verified, especially since procaine is no longer marketed in in the US as a single ingredient product. No information is available on the use of procaine during breastfeeding. Based on the short half-life of procaine in the plasma and the low excretion of other local anesthetics into breastmilk, a single dose of procaine during breastfeeding is unlikely to adversely affect the breastfed infant. However, an alternate drug may be preferred, especially while nursing a newborn or preterm infant. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. |
| References |
[1]. Fan, P. and F.F. Weight, Procaine impairs the function of 5-HT3 receptor-ion channel complex in rat sensory ganglion neurons. Neuropharmacology, 1994. 33(12): p. 1573-9. [2]. Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res, 2003. 63(16): p. 4984-9. [3]. Adamec, R.E. and C. Stark-Adamec, The effects of procaine HCl on population cellular and evoked response activity within the limbic system of the cat. Evidence for differential excitatory action of procaine in a variety of limbic circuits. Prog Neuropsychopharmacol Biol Psychiatry, 1987. 11(4): p. 345-64. |
| Additional Infomation |
Procaine is a benzoate ester, formally the result of esterification of 4-aminobenzoic acid with 2-diethylaminoethanol but formed experimentally by reaction of ethyl 4-aminobenzoate with 2-diethylaminoethanol. It has a role as a local anaesthetic, a central nervous system depressant, a peripheral nervous system drug and a drug allergen. It is a benzoate ester, a substituted aniline and a tertiary amino compound. It is functionally related to a 2-diethylaminoethanol and a 4-aminobenzoic acid. It is a conjugate base of a procaine(1+). A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). Procaine has also been investigated as an oral entry inhibitor in treatment-experienced HIV patients. Procaine is a benzoic acid derivative with local anesthetic and antiarrhythmic properties. Procaine binds to and inhibits voltage-gated sodium channels, thereby inhibiting the ionic flux required for the initiation and conduction of impulses. In addition, this agent increases electrical excitation threshold, reduces rate of rise of action potential and slows nerve impulse propagation thereby causing loss of sensation. Procaine is only found in individuals that have used or taken this drug. It is a local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [PubChem]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. A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). See also: Procaine Hydrochloride (has salt form); Penicillin G Procaine (is active moiety of); Procaine Merethoxylline (has salt form) ... View More ... Drug Indication Used as a local anesthetic primarily in oral surgery Mechanism of Action 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/ |
Solubility Data
| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~423.17 mM) H2O : ~1 mg/mL (~4.23 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.5 mg/mL (10.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 4: 2 mg/mL (8.46 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C). (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.2317 mL | 21.1586 mL | 42.3173 mL | |
| 5 mM | 0.8463 mL | 4.2317 mL | 8.4635 mL | |
| 10 mM | 0.4232 mL | 2.1159 mL | 4.2317 mL |