Prlocaine has a greater inhibitory impact on the plasma membrane Na,K-ATPase of transformed fibroblasts (LM cells) at 37 °C (43.8 mM) than it does at 25 °C (28.2 mM) [2].

Absorption, Distribution and Excretion
Prilocaine is metabolized in the liver and kidneys and excreted via the kidneys. /About/ Hydrolysis of the amide bond in prilocaine… After intravenous injection in cats, the plasma concentration of the R-(-)-enantiomer was found to be lower than that of the S-(+)-enantiomer. In vitro studies using liver preparations from various mammals confirmed that the hydrolysis rate of the R-(-)-isomer was much higher than that of the S-(+)-isomer… The D-(-)-isomer is more likely to cause methemoglobinemia, possibly due to the higher blood concentration of its hydrolysis product, o-toluidine.
Primocaine fetal/maternal concentration ratio: 1.0 /From table/
Intravenous injection of 0.2 g primocaine resulted in a plasma concentration of 0.26 mg/dL after 0.3 hours and 0.14 mg/dL after 0.17 hours; intravenous injection of 0.4 g resulted in a plasma concentration of 0.15 mg/dL at 0.12 hours and 0.08 mg/dL at 0.33 hours; epidural block injection of 0.4 g resulted in a peak plasma concentration of 0.26 mg/dL at 0.25 hours; intercostal block injection resulted in a plasma concentration of 0.40 mg/dL at 0.25 hours. /From table/

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Metabolism/Metabolites
Amide local anesthetics are typically degraded in the hepatic endoplasmic reticulum, with initial reactions involving N-dealkylation and subsequent hydrolysis. However, for prilocaine, the initial step is hydrolysis, producing the o-toluidine metabolite, which can lead to methemoglobinemia.
Biotransformation of prilocaine… in rats administered o-toluidine and N-alanine.

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Biological half-life
Intravenous infusion of 250 mg mepivacaine hydrochloride (I-HCl) and prilocaine hydrochloride (II-HCl) into healthy volunteers. The half-life of I is generally longer than that of II; the systemic clearance of II is consistently higher than that of I. The clearance of II exceeds normal hepatic blood flow: presumably an extrahepatic metabolic site exists.

Interactions
...Mouse studies have shown increased toxicity when co-administered with tetracaine. ...Primocaine has been reported to interact with succinylcholine, leading to an increase in the intensity and duration of succinylcholine-induced neuromuscular blockade and respiratory depression; other depolarizing muscle relaxants (e.g., decylamine) and non-depolarizing muscle relaxants (e.g., gallium triiodide and pancuronium bromide) may have similar effects. ...Primocaine slightly enhances the neuromuscular blocking intensity of acuronium chloride. A significant decrease in tidal volume was observed, indicating respiratory depression... ...Adrenaline prolongs the duration of action of primocaine. /Primocaine Hydrochloride/ ...For more complete data on interactions of primocaine (15 in total), please visit the HSDB records page.

[1]. Neurotoxic effects of local anesthetics on the mouse neuroblastoma NB2a cell line. Biotech Histochem. 2015 Apr;90(3):216-22.

[2]. Effects of local anaesthetics on the activity of the Na,K-ATPase of canine renal medulla. Pharmacol Res. 2000 Jan;41(1):1-7.

Prilocaine is an amino acid amide composed of an amide bond formed by the combination of N-propyl-DL-alanine and 2-methylaniline, and is used as a local anesthetic. It has dual effects of local anesthesia and anticonvulsant action. Prilocaine is an amino acid amide and a monocarboxylic acid amide. It is a local anesthetic with pharmacological effects similar to lidocaine. Currently, it is most commonly used for infiltration anesthesia in dentistry. (Excerpt from JAMA Drug Evaluation Yearbook, 1992, p. 165) Prilocaine is an amide-type local anesthetic. The physiological effect of prilocaine is achieved through local anesthesia. Prilocaine is a toluidine derivative, a medium-acting aminoamide with local anesthetic properties. Prilocaine stabilizes neuronal membranes by preferentially binding to and inhibiting the depolarization of voltage-gated sodium channels. This leads to decreased cell membrane permeability, thereby inhibiting the sodium ion influx required for the initiation and conduction of nerve impulses. A local anesthetic with pharmacological effects similar to lidocaine. Currently, it is most commonly used for infiltration anesthesia in dentistry. See also: Primacaine Hydrochloride (salt form)... See more...

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Drug Indications
Used as a local anesthetic, commonly used in dentistry.

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Mechanism of Action
Primacaine acts on sodium ion channels on the neuronal cell membrane, limiting the spread of epileptic activity and reducing the propagation of seizures. Its antiarrhythmic effect is achieved by affecting sodium channels in Purkinje fibers.
...Blocking nerve conduction may be achieved by competing with calcium ions (CA) for a site controlling membrane permeability... Calcium ions also participate in the effects of local anesthetics on smooth muscle and adrenal medulla... /Local Anesthetics/
...Inhibits the generation and conduction of nerve impulses. Their primary site of action is the cell membrane. ...Blocking conduction by reducing or preventing a transient, significant increase in the permeability of the excitatory membrane to sodium ions (Na+), an increase usually caused by slight membrane depolarization. Local Anesthetics: As the effect of the anesthetic in the nerve gradually increases, the electrical excitation threshold rises, and the conduction safety factor decreases; when this effect is fully realized, nerve conduction is blocked. Local anesthetics have two mechanisms of action: one is to achieve blockade by increasing the surface pressure of the lipid layer that makes up the nerve membrane, thereby closing the pores through which ions can pass. The other is to affect membrane permeability by increasing the degree of membrane disturbance. /Local Anesthetics/

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Therapeutic Uses
Local Anesthetics
A drug with a chemical structure similar to lidocaine and mepivacaine, used for local and regional block anesthesia. Its onset time and efficacy (1-3% solution) are comparable to those of lidocaine and mepivacaine at concentrations of 1%-2%. Its duration of action is between that of short-acting lidocaine and long-acting mepivacaine. /Primocaine Hydrochloride/
Primocaine hydrochloride…has been used for…spinal anesthesia. /Primocaine Hydrochloride/
...acts on any part of the nervous system and all types of nerve fibers. /Local Anesthetics/
For more complete data on the therapeutic uses of primocaine (10 in total), please visit the HSDB record page.

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Drug Warnings
As with other local anesthetics, prilocaine hydrochloride is contraindicated in patients with shock, severe cardiovascular disease, or cardiac conduction block. /Prilocaine Hydrochloride/
...It should not be given to patients with idiopathic or congenital methemoglobinemia, anemia, or heart failure or respiratory failure with hypoxia; due to the cumulative effect of hemoglobin elevation from a single dose, caution should be exercised when using it for continuous epidural anesthesia. /Prilocaine Hydrochloride/
In cases of bleeding, the sympathetic blockade caused by epidural anesthesia can become extremely pronounced and may lead to rapid and harmful circulatory changes. /Local Anesthetics/
The two main dangers of tail anesthesia are: (1) accidental needle insertion into the sacral venous plexus, resulting in intravascular injection of the drug; (2) needle penetration of the dura mater, resulting in high spinal anesthesia. /Local Anesthetics/
For more drug warnings (complete) data on prilocaine (16 in total), please visit the HSDB record page.

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Pharmacodynamics
Primacaine binds to the intracellular surface of sodium channels, blocking the influx of sodium ions into the cell. Therefore, action potential conduction and nerve function are inhibited. This blockade is reversible; once the drug diffuses out of the cell, sodium channel function and nerve conduction are restored.

C13H20N2O

220.32

220.157

721-50-6

Prilocaine hydrochloride;1786-81-8;Prilocaine acetate

4906

White to off-white solid powder

1.0±0.1 g/cm3

361.6±25.0 °C at 760 mmHg

37-38ºC

134.3±23.3 °C

0.0±0.8 mmHg at 25°C

1.543

1.74

2

2

5

16

218

0

MVFGUOIZUNYYSO-UHFFFAOYSA-N

InChI=1S/C13H20N2O/c1-4-9-14-11(3)13(16)15-12-8-6-5-7-10(12)2/h5-8,11,14H,4,9H2,1-3H3,(H,15,16)

N-(2-methylphenyl)-2-(propylamino)propanamide

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

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

DMSO : ~100 mg/mL (~453.91 mM)
H2O : ~2.5 mg/mL (~11.35 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.35 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.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.35 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.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (11.35 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.

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Solubility in Formulation 4: 50 mg/mL (226.95 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication.

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