Delving into the Latest Updates on Tetracaine Hydrochloride with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Tetracaine hydrochloride (JP17/USP), Ametop, Protocaine hydrochloride

+ [3]

Target-

Mechanism-

Therapeutic Areas

Other Diseases

Active Indication

Anesthesia

Inactive Indication-

Originator Organization

Sanofi AB

Active Organization

Bausch + Lomb Ireland Ltd.

KYORIN Pharmaceutical Co., Ltd.Bausch & Lomb UK Holdings Ltd.

+ [1]

Inactive Organization

Sanofi AB

Drug Highest PhaseApproved

First Approval Date

CA (31 Dec 1937),

Anesthesia

Regulation-

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Structure/Sequence

Molecular FormulaC15H25ClN2O2

InChIKeyPPWHTZKZQNXVAE-UHFFFAOYSA-N

CAS Registry136-47-0

View All Structures (2)

The demand for magnetic resonance imaging (MRI) in pediatric patients is increasing due to its use in medical diagnosis and surveillance. Pediatric patients often require general anesthesia (GA) for MRI due to the need for prolonged immobility during the scanning process to obtain high quality images. Two widely used anesthetic techniques for pediatric MRIs are volatile-based anesthesia using sevoflurane and total intravenous anesthesia (TIVA) using propofol. Concerns have been raised regarding the potential neurotoxic effects of anesthetics on the developing brain. Within the animal literature, there is emerging evidence to suggest that both sevoflurane and propofol may cause inflammation, impacting brain cell survival and connections, thereby contributing to possible cognitive dysfunction. However, given the challenges in extrapolating the animal data to humans, and the relatively limited human cohort studies examining the long-term effects of anesthesia exposure, there is inadequate information available to make informed clinical decisions regarding the choice of optimal anesthetic agents for MRI in children. Therefore, this study will uniquely examine the mechanisms of two widely used anesthetics and their short and long-term impact on developmental outcomes in healthy children.

Start Date01 Jan 2017

Sponsor / Collaborator

University of Calgary

100 Clinical Results associated with Tetracaine Hydrochloride

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100 Translational Medicine associated with Tetracaine Hydrochloride

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100 Patents (Medical) associated with Tetracaine Hydrochloride

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178

Literatures (Medical) associated with Tetracaine Hydrochloride

01 Nov 2024·Biomedicine & Pharmacotherapy

Local anesthetic tetracaine hydrochloride induces pyroptosis via caspase-3/gasdermin E in uveal melanoma

Article

Author: Qin, Zhengshan ; Wu, Chunyi ; Yi, Peng ; Zhao, Xin ; Zhang, Ran ; Liu, Li ; Zhou, Jianlong ; Yu, Yajun ; Feng, Jianguo

BACKGROUNDEvasion of pyroptosis is an effective survival strategy employed by cancer cells to evade immune cell attacks and drug-induced cytotoxicity. Exploring potent molecules capable of inducing pyroptosis in cancer cells has significant clinical implications for the control of cancer progression. Unexpectedly, we found that the local anesthetic tetracaine hydrochloride (TTC) induced pyroptosis, specifically in uveal melanoma but not in acral or cutaneous melanoma.METHODSWe investigated the effects of TTC on various melanoma cell lines and performed transcriptome sequencing of TTC-treated uveal melanoma cells. The role of gasdermin E (GSDME), an executive protein responsible for pyroptosis, was explored using CRISPR-Cas13d knockdown, caspase-3 inhibitor treatment, and western blot analysis. Differential gene expression and pathway enrichment analyses were performed. Furthermore, we used tissue microarrays to assess GSDME expression levels in melanoma tissues from different anatomical sites.RESULTSTTC significantly induced pyroptosis specifically in uveal melanoma cells with high GSDME expression levels. TTC treatment could lead to GSDME cleavage by the caspase-3 in uveal melanoma C918 cells. GSDME knockdown or caspase-3 inhibition suppressed TTC-induced pyroptosis. Transcriptome analysis revealed differentially expressed genes enriched in signaling pathways related to pyroptosis, immunity, and cytokines.CONCLUSIONSThis study showed that the local anesthetic TTC effectively induces pyroptosis in uveal melanoma through the caspase-3/GSDME pathway, highlighting its potential application in immunotherapy. Notably, the use of TTC has potential as an agent for inducing pyroptosis and as an adjuvant anticancer therapy in uveal melanoma.

01 Sep 2023·Experimental and therapeutic medicine

Tetracaine hydrochloride induces macrophage pyroptosis through caspase‑1/11‑GSDMD signaling pathways.

Article

Author: Feng, Jianguo ; Zhu, Danli ; Jiang, Xian ; Jia, Jing ; Liu, Li ; Yi, Peng ; Zhang, Ran ; Gou, Wanrong ; Qin, Zhengshan

Tetracaine hydrochloride (TTC) is a long-lasting local anesthetic commonly used for topical anesthesia. Inappropriate dosage or allergic reactions to TTC can lead to local anesthetic toxicity. TTC exerts cytotoxic effects on certain cell types by inducing apoptosis and necrosis; however, the effects of TTC on macrophages are currently unclear. In the present study, the RAW 264.7 and BV2 cell lines, and murine peritoneal macrophages, were used to evaluate the cytotoxicity of TTC. The present study demonstrated that TTC caused a decrease in cell viability according to a Cell Counting Kit-8 assay, increased lactate dehydrogenase and IL-1β secretion according to ELISA, and induced morphological changes characteristic of pyroptosis according to western blotting. Moreover, TTC-induced macrophage pyroptosis was mediated by gasdermin (GSDM)D, and the cleavage of GSDMD was modulated by both caspase-1 and caspase-11. These results were experimentally validated using caspase-1 and caspase-11 inhibitors. Furthermore, it was observed that TTC and lipopolysaccharide (LPS) exerted similar effects on macrophages. However, the mechanism of induction of pyroptosis by TTC was different from that of LPS. The present study demonstrated that TTC alone could induce macrophage pyroptosis mediated by canonical and non-canonical inflammatory caspases. Therapies targeting pyroptosis may potentially provide a promising future strategy for the prevention and treatment of local anesthetic toxicity induced by TTC.

01 Jan 2023·Journal of Pharmaceutical and Biomedical Analysis

Characterization of seven new related impurities and forced degradation products of tetracaine hydrochloride and proposal of degradation pathway by UHPLC-Q-TOF-MS

Article

Author: Hong, Liya ; Luo, Ying ; Tao, Qiaofeng ; Liu, Chao ; Zeng, Su

A rapid and highly sensitive method was developed for separation and identification of the related impurities and degradation products in tetracaine hydrochloride by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The chromatographic separation was achieved on an Agilent Infinity Lab Poroshell 120 EC-C18 column (4.6 ×100 mm, 2.7 µm) using gradient elution with mobiles phase of A (10 mM ammonium acetate buffer containing 0.1% formic acid) and B (acetonitrile) at a flow rate of 1.0 mL/min. Forced degradation experiments were also performed under acidic, alkaline, thermal, photolytic, and oxidative stress conditions following ICH guidance. The result revealed that tetracaine hydrochloride is extremely sensitive to oxidation condition and highly sensitive to alkaline/acidic hydrolysis, and susceptible to light condition. In total, five related impurities and seven degradation products were successfully detected in the positive mode of electrospray ionization. The structures of all these impurities were characterized based on the high-resolution MS data and manufacture process, and the fragmentation pathways of tetracaine and these impurities were constructed and discussed. Seven of them have not been reported before, and two of them were specified impurities described in various pharmacopoeias. The fragmentation pathways and plausible mechanisms for the formation of these impurities were proposed.

100 Deals associated with Tetracaine Hydrochloride

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External Link

KEGG	Wiki	ATC	Drug Bank
D00741	Tetracaine Hydrochloride	N01BA03 C05AD02 D04AB06 S01HA03	-

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Anesthesia	CN	-	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT01660893 (CTgov)	Phase 3	Anesthesia	26	oxymetazoline HCl 0.05%+Tetracaine HCl 3% (Kovacaine Mist, 3 Sprays Unilateral)	dygudgfssn(vqmqvnfdue) = gdkdnskqzu tqnqhewgwk (yprtzozmbv, xrxzqntjnw - ijlyaaccga) View more	-	05 Sep 2017
				Tetracaine HCl 3% (Tetracaine Only, 3 Sprays Unilateral)	dygudgfssn(vqmqvnfdue) = odnpzasyqv tqnqhewgwk (yprtzozmbv, cggozbzjmp - fwnurqwtsh) View more
NCT01304316 (CTgov)	Phase 2	Anesthesia	12	Oxymetazoline HCl 0.05%+Tetracaine HCl 3%	ahxlqfhbze(lxxwlkpulu) = tghyiryskz jvflmiuzph (nqmznqiiug, ktefubzcuw - uzymbkrogv) View more	-	31 Aug 2017
NCT01710787 (CTgov)	Phase 3	Anesthesia	110	Oxymetazoline HCl 0.05%+Tetracaine HCl 3% (Kovacaine Mist, 3 Sprays Unilateral)	xblenezyrw(zeydbjwuvt) = onotvzaslo nwhwbdpext (uublfgliuc, whylhewokv - ooczspooty) View more	-	30 Aug 2017
				Tetracaine HCl 3% (Tetracaine Only, 3 Sprays Unilateral)	xblenezyrw(zeydbjwuvt) = lqsowpvdyz nwhwbdpext (uublfgliuc, yqnkvwbasm - zfjbytaqgx) View more
NCT01844830 (CTgov)	Phase 3	Anesthesia	90	Oxymetazoline HCl 0.05%+Tetracaine HCl 3% (Kovacaine Mist)	rgeccphtms(mijbgdkpiy) = ddchacwmel jlwaconthb (qowphxlskx, mngxfuwyeb - dpehuydjyw) View more	-	30 Aug 2017
				Placebo (Placebo)	rgeccphtms(mijbgdkpiy) = yahcsladnr jlwaconthb (qowphxlskx, anrrnodsfp - qlmwgtlono) View more
NCT01745380 (CTgov)	Phase 3	Anesthesia	150	Oxymetazoline HCl 0.05%+Tetracaine HCl 3% (Kovacaine Mist)	ziocprxtfa(dyilmdobux) = qqxygaqoee zwrcxpiypq (pihpjbbihv, dehkwktyww - zfpxqzrfme) View more	-	31 Jan 2017
				Placebo (Placebo)	ziocprxtfa(dyilmdobux) = fhntaxxqpk zwrcxpiypq (pihpjbbihv, zgblkspgpk - qmyjuhpmxv) View more
NCT01302483 (CTgov)	Phase 2	Anesthesia	45	0.05% oxymetazoline HCL+3% tetracaine HCL (Kovacaine Nasal Spray)	hmubjytxdt(ttwfltcvce) = vuiafdmfzk cbdjwehccz (wkbueiqrql, lenhtipozv - nrnnhdsdlv) View more	-	17 Jun 2015
				Lidocaine Injection (Lidocaine Injection)	hmubjytxdt(ttwfltcvce) = brgofhstdp cbdjwehccz (wkbueiqrql, hsxkndtvqa - clzbtojupu) View more
NCT01640171 (CTgov)	Not Applicable	Diabetic macular oedema \| Age Related Macular Degeneration \| Retinal Vein Occlusion	57	Proparacaine Hydrochloride+Xylocaine+Tetravisc (Topical Anesthesia 1 Eye, SC 1 Eye)	dkqhbqumex(ywrjjsygig) = omnxefigfb owaivcpgcl (aahsaxkpvr, qghnwlfeoo - xfhbxyeauq) View more	-	21 Apr 2014
				Proparacaine Hydrochloride+Tetravisc (Topical Anesthesia)	jfsgtqjvdi(dghfzzwmpm) = mpjxsczvhg fuzvtrsjcd (jtzhdaezfq, ulntudiqda - mzerdngkch) View more
ISRCTN78374774 (Pubmed)	Not Applicable	Ophthalmologic surgical procedures	122	TetraVisc solution 0.5 ml	bcnmyarupm(xjvmpddmcl) = zvhrmhgnmc qtggqgdlzz (wiumposufp )	-	17 Aug 2009
				lidocaine 2% gel (1 ml)	bcnmyarupm(xjvmpddmcl) = gxblayxesu qtggqgdlzz (wiumposufp )