Procaine hydrochloride (0.01-100 microM) reduced the 5-HT3 receptor-mediated inward current in the whole-cell patch clamp recording. Procaine appears to produce a competitive inhibition on 5-HT3 receptors with a KD of 1.7 microM[1]. is a DNA-demethylating chemical that produces a 40% reduction in 5-methylcytosine DNA concentration as assessed by high-performance capillary electrophoresis or total DNA enzyme digestion. Procaine can also demethylate heavily hypermethylated CpG islands. Procaine also exhibits growth-inhibitory actions in malignant cancer cells, producing mitotic arrest[2]. Procaine serves as an excitant of limbic system cells, and that procaine changes synaptic transmission in some, but not all, output pathways from the amygdale[3].

Procaine is an excitant of limbic system cells. 15 mg/kg Procaine increases cellular activity in amygdala ventral hippocampus, nucleus accumbens, temporal neocortex and ventromedial hypothalamus of awaken cat. Procaine facilitates transmission of evoked excitatory activity from the amygdala to the ventromedial hypothalamus. Procaine influences frequency and amplitude of reticularly elicited hippocampal rhythmical slow activity. Procaine (0.5 μL, 20% wt/vol) injected at points in the ascending system anterior to the supramamillary nucleus, in the region of the medial forebrain bundle or in the medial septum, reduces the amplitude of reticularly elicited rhythmical slow activity (RSA) but has no effect on its frequency. Procaine injected at points in the ascending system from just anterior to the reticular formation stimulation site, up to, and including the supramamillary nucleus, reduces both the frequency and amplitude of reticularly elicited RSA. Procaine (80mg/kg) increases the duration and propagation of epileptiform afterdischarges (ADs) produced by electrical stimulation of the amygdala in rats. Porcaine also increases the rate of seizure development (kindling) produced by repeated stimulation of the amygdala. Procaine would itself act as convulsants in well kindled subjects. Procaine produces a weak but significant increase in the amplitude of the transcallosal evoked potential. Procaine influences generation of auditory brain stem responses (ABRs). Procaine (30 μL of 1% solution) injection into the trapezoid body of guinea pig affects many of the components of the scalp-derived ABR: N2 is delayed making P2 broader in duration, P3 and N3 are lost, P4 is shortened in latency, broadened in duration but unaffected in amplitude, and N4 is considerably attenuated. Only P1 and N1 are unaffected by the procaine injection. Procaine increases the therapeutic index of cisplatin by improving antitumor activity of cisplatin and reducing its nephrotoxicity. Simultaneous administration of cisplatin and Procaine (40 mg/kg) to BDF1 mice produces 50% lethal dose (LD50) and 90% lethal dose (LD90) values approximately two times higher than those observed with cisplatin alone. Simultaneous administration produces a higher cure rates compared with cisplatin alone (50% vs 9%). The increased blood urea nitrogen (BUN) levels observed 4-7 days following a single administration of cisplatin, as well as the tubular degenerative changes detected by light microscopy, are not observed when the same doses of cisplatin are given simultaneously with Procaine.

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.

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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

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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 Summary
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.

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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.

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Toxicity Data
LD50: 350 mg/kg (Oral, mouse).

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Interactions
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.

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Non-Human Toxicity Values
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

[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.

Therapeutic Uses
Anesthetics, Local
PROCAINE SOLN ARE USED FOR INFILTRATION ANESTHESIA ..., NERVE BLOCK ..., & SPINAL ANESTHESIA (DOSE VARIES WITH TECHNIC EMPLOYED). FOR CONTINUAL CAUDAL ANALGESIA ... /HYDROCHLORIDE/
OBJECTIVE OF CONTINUOUS SPINAL ANESTHESIA IS TO ... PRODUCE LEVEL, DEGREE, & DURATION OF ANESTHESIA DESIRED. ... LOCAL ANESTHETIC OF SHORT DURATION, SUCH AS PROCAINE, CAN BE USED TO INCR CONTROLLABILITY FURTHER.
/Procaine hydrochloride/ is injected locally adjacent to the muscle cone ... or in the region of the facial nerve ... to reduce pain and to prevent eye and lid movements during surgery. ... Used to block nerve endings in the immediate area of surgery (infiltration anesthesia) for procedures such as minor lid operations. /Procaine hydrochloride/
For more Therapeutic Uses (Complete) data for PROCAINE (14 total), please visit the HSDB record page.

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Drug Warnings
MAJOR CAUSE OF SYSTEMIC REACTIONS TO LOCAL ANESTHETICS IS HIGH BLOOD CONCN OF DRUG. ... BECAUSE OF THREAT OF HIGH BLOOD CONCN ... IT IS IMPORTANT TO ADMIN SMALLEST AMT THAT WILL BE EFFECTIVE. /LOCAL ANESTHETICS/
EXTREMELY RARE EVENT IS ACCIDENTAL INJECTION OF LOCAL ANESTHETIC DIRECTLY INTO FETUS; THIS RESULTS IN APNEA, BRADYCARDIA, & CONVULSIONS IN FIRST MIN OF LIFE.
Since aminobenzoic acid, a metabolite of procaine, may antagonize the activity of aminosalicylic acid and sulfonamides, some clinicians have suggested procaine should not be used in patients receiving these drugs. IV administration of procaine hydrochloride is contraindicated in patients with myasthenia gravis or in those patients receiving digitalis, anticholinesterase drugs, or succinylcholine.
High plasma concentrations of local anesthetics affect the CNS and cardiovascular system. Generally, high plasma concentrations of the drugs initially produce CNS stimulatory effects manifested by anxiety, apprehension, restlessness, nervousness, disorientation, confusion, dizziness, blurred vision, tremors, twitching, shivering, and seizures, followed by CNS depression manifested of drowsiness, unconsciousness, and respiratory arrest. Nausea, vomiting, chills, miosis, and tinnitus may also occur. /Local anesthetics/
For more Drug Warnings (Complete) data for PROCAINE (15 total), please visit the HSDB record page.

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Pharmacodynamics
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.

C13H20N2O2.HCL

272.77

272.129

51-05-8

Procaine;59-46-1;Procaine-d4 hydrochloride

4914

White to off-white solid powder

195-196°C 17mm

155-156 °C(lit.)

195-196°C/17mm

3.15

1

4

7

17

222

0

MFDFERRIHVXMIY-UHFFFAOYSA-N

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

2-(diethylamino)ethyl 4-aminobenzoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light.  (2). This product is not stable in solution, please use freshly prepared working solution for optimal results.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 130 mg/mL (476.59 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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 (Please use freshly prepared in vivo formulations for optimal results.)