The pH-Dependent Local Anesthetic Activity of Diethylaminoethanol, a Procaine Metabolite

Butterworth, John F.; Lief, Philip A.; Strichartz, Gary R.

doi:10.1097/00000542-198804000-00005

Cited by 12 publications

(6 citation statements)

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“…This value was almost comparable to those (2-5 mM) obtained by other investigators [248,249] in the same preparation and also to that (ca. 1 mM) reported previously in the rat sciatic nerve [248]. Moreover, a ratio of the procaine's IC 50 value to that of lidocaine (0.74 mM; [19]) for frog CAP inhibition was comparable to a ratio of procaine concentration (0.53%), needed for 50% motor nerve conduction block, to lidocaine's one (0.14%) in rats [250].…”

Section: Local Anestheticssupporting

confidence: 92%

“…A well-known another ester-type local anesthetic procaine [247] reversibly reduced frog sciatic nerve CAP peak amplitudes in a concentration range of 0.1-5 mM with an IC 50 value of 2.2 mM [27]. This value was almost comparable to those (2-5 mM) obtained by other investigators [248,249] in the same preparation and also to that (ca. 1 mM) reported previously in the rat sciatic nerve [248].…”

Section: Local Anestheticssupporting

confidence: 76%

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Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

Kumamoto

2020

Pharmaceuticals

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Nociceptive information is transmitted from the periphery to the cerebral cortex mainly by action potential (AP) conduction in nerve fibers and chemical transmission at synapses. Although this nociceptive transmission is largely inhibited at synapses by analgesics and their adjuvants, it is possible that the antinociceptive drugs inhibit nerve AP conduction, contributing to their antinociceptive effects. Many of the drugs are reported to inhibit the nerve conduction of AP and voltage-gated Na+ and K+ channels involved in its production. Compound action potential (CAP) is a useful measure to know whether drugs act on nerve AP conduction. Clinically-used analgesics and analgesic adjuvants (opioids, non-steroidal anti-inflammatory drugs, α2-adrenoceptor agonists, antiepileptics, antidepressants and local anesthetics) were found to inhibit fast-conducting CAPs recorded from the frog sciatic nerve by using the air-gap method. Similar actions were produced by antinociceptive plant-derived chemicals. Their inhibitory actions depended on the concentrations and chemical structures of the drugs. This review article will mention the inhibitory actions of the antinociceptive compounds on CAPs in frog and mammalian peripheral (particularly, sciatic) nerves and on voltage-gated Na+ and K+ channels involved in AP production. Nerve AP conduction inhibition produced by analgesics and analgesic adjuvants is suggested to contribute to at least a part of their antinociceptive effects.

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Section: Local Anestheticssupporting

confidence: 92%

Section: Local Anestheticssupporting

confidence: 76%

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

Kumamoto

2020

Pharmaceuticals

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“…The different behavior of procaine might be attributed to the pharmacological effects of its cleavage products. Procaine is cleaved into the two metabolites diethylaminoethanol (DEAE) and para-aminobenzoic acid (PABA), each with specific pharmacological effects, e.g., DEAE has a vasodilatory effect [30].…”

Section: Discussionmentioning

confidence: 99%

Uterine contractility changes in a perfused swine uterus model induced by local anesthetics procaine, lidocaine, and ropivacaine

Weinschenk¹,

Dittrich²,

Müller³

et al. 2018

PLoS ONE

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BackgroundLocal anesthetics (LAs) are increasingly used as therapeutics due to their multiple molecular effects. They may be potential agents also in gynecology and reproductive medicine. The objective of this study was to investigate the contractility response of the perfused swine uterus to different concentrations of the LAs procaine, lidocaine, and ropivacaine.Methods and findingsIn an extracorporeal perfusion model with fresh swine uteri, effects of administered boli of these three LAs in concentrations of 0.1 mg/mL, 0.5 mg/mL and 1.0 mg/mL on uterine contractility and peristalsis were assessed using an intrauterine double-chip micro-catheter. A dose-dependent increase in intrauterine pressure (IUP) in the isthmus and corpus uteri was observed after the administration of the ester-LA procaine 0.1, 0.5, and 1.0%, which was not seen with lower concentrations, or buffer solution. An increase-decrease curve was found after increasing concentrations of the amide-LA lidocaine and ropivacaine, with an IUP plateau with 0.1 and 0.5%, and a decrease with 1% (p<0.01). All reactions were seen in both the isthmus and corpus uteri. The difference of the contractility pattern between ester- and amide-LA at 1% concentration was significant.ConclusionLAs dose-dependently modulate contractility in non-pregnant swine uteri. The amid-LAs lidocaine and ropivacaine reduce contractility in higher concentrations and may be used as therapeutics in disorders with increased uterine contractility, as dysmenorrhoea, endometriosis, and infertility. The multiple molecular effects of LAs may explain these effects. This in-vitro pilot study in vitro provides initial data for designing further studies to transfer the results onto humans.

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“…In different organs, procaine is hydrolyzed under the microsomal carboxylesterases [ 51 , 52 ]. DEAE displays local anesthetic activity [ 53 ].…”

Section: Procaine Pharmacokinetics and Metabolismmentioning

confidence: 99%

Procaine–The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects

Grădinaru

Ungurianu

Margină

et al. 2021

Oxidative Medicine and Cellular Longevity

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Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an “anti-aging” molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a “veteran” drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database.

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The pH-Dependent Local Anesthetic Activity of Diethylaminoethanol, a Procaine Metabolite

Cited by 12 publications

References 0 publications

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

Inhibition of Fast Nerve Conduction Produced by Analgesics and Analgesic Adjuvants—Possible Involvement in Pain Alleviation

Uterine contractility changes in a perfused swine uterus model induced by local anesthetics procaine, lidocaine, and ropivacaine

Procaine–The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects

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