Chloroprocaine

{{Short description|Local anesthetic medication}} {{Use dmy dates|date=December 2024}} {{cs1 config |name-list-style=vanc |display-authors=6}} {{Infobox drug | Verifiedfields = changed | verifiedrevid = 460032727 | image = Chloroprocaine.svg | image_class = skin-invert-image | width = 250 | alt = | caption =

| pronounce = | tradename = Nesacaine, others | Drugs.com = {{ubl | Hcl: {{drugs.com|monograph|chloroprocaine-hydrochloride}} | Ophthalmic: {{drugs.com|mtm|chloroprocaine-ophthalmic}} }} | MedlinePlus = | DailyMedID = Chloroprocaine | pregnancy_AU =  | pregnancy_AU_comment = | pregnancy_category = | routes_of_administration = Intrathecal, eye drop | class = Local anesthetic | ATC_prefix = N01 | ATC_suffix = BA04 | ATC_supplemental = {{ATC|S01|HA08}}

| legal_AU =  | legal_AU_comment = | legal_BR =  | legal_BR_comment = | legal_CA = Rx-only | legal_CA_comment = <ref name="Clorotekal CA RDS">{{cite web | title=Regulatory Decision Summary for Clorotekal | website=Drug and Health Products Portal | date=22 August 2024 | url=https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS1733408271619 | access-date=27 December 2024}}</ref> | legal_DE =  | legal_DE_comment = | legal_NZ =  | legal_NZ_comment = | legal_UK =  | legal_UK_comment = | legal_US = Rx-only | legal_US_comment = <ref name="Nesacaine FDA label">{{cite web | title=Nesacaine- chloroprocaine hydrochloride injection, solution; Nesacaine MPF- chloroprocaine hydrochloride injection, solution | website=DailyMed | date=1 September 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a844e68a-1462-40e4-be5e-f56214906eb9 | access-date=21 January 2023}}</ref><ref name="Iheezo FDA label" /><ref name="Clorotekal FDA label">{{cite web | title=Clorotekal- chloroprocaine hydrochloride injection, solution | website=DailyMed | date=4 December 2020 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=90f7a095-f6db-456b-951f-9aee54c5dbc0 | access-date=27 December 2024}}</ref> | legal_EU = | legal_EU_comment = | legal_UN =  | legal_UN_comment = | legal_status = Rx-only<ref>{{cite web |url=https://www.ema.europa.eu/en/documents/psusa/chloroprocaine-hydrochloride-list-nationally-authorised-medicinal-products-psusa00010078202203_en.pdf |title=List of nationally authorised medicinal products Active substance(s): chloroprocaine hydrochloride |publisher=European Medicines Agency |date=27 October 2022 |access-date=10 August 2025}}</ref>

| CAS_number_Ref = {{cascite|correct|??}} | CAS_number = 133-16-4 | CAS_number2 = 3858-89-7 | CAS_supplemental = | PubChem = 8612 | PubChem2 = 441348 | IUPHAR_ligand = 7145 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB01161 | DrugBank2 = DBSALT000823 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 8293 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = 5YVB0POT2H | UNII2 = LT7Z1YW11H | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D07678 | KEGG2 = D00732 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 3636 | ChEBI2 = 3637 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1179047 | ChEMBL2 = 944 | NIAID_ChemDB = | PDB_ligand = | synonyms =

| IUPAC_name = 2-diethylaminoethyl-4-amino-2-chloro-benzoate | C=13 | H=19 | Cl=1 | N=2 | O=2 | SMILES = CCN(CC)CCOC(=O)C1=C(Cl)C=C(N)C=C1 | SMILES2 = Cl.CCN(CC)CCOC(=O)C1=C(Cl)C=C(N)C=C1 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C13H19ClN2O2/c1-3-16(4-2)7-8-18-13(17)11-6-5-10(15)9-12(11)14/h5-6,9H,3-4,7-8,15H2,1-2H3 | StdInChI2 = 1S/C13H19ClN2O2.ClH/c1-3-16(4-2)7-8-18-13(17)11-6-5-10(15)9-12(11)14;/h5-6,9H,3-4,7-8,15H2,1-2H3;1H | StdInChI_comment = | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VDANGULDQQJODZ-UHFFFAOYSA-N | StdInChIKey2 = SZKQYDBPUCZLRX-UHFFFAOYSA-N | density = | density_notes = | melting_point = | melting_high = | melting_notes = | boiling_point = | boiling_notes = | solubility = | sol_units = | specific_rotation = }}

'''Chloroprocaine''', sold under the brand name '''Nesacaine''' among others is a local anesthetic given by injection.<ref name="Nesacaine FDA label" /> It is used as the hydrochloride salt.<ref name="Clorotekal FDA label" /> Chloroprocaine is a local anesthetic.<ref name="Nesacaine FDA label" /><ref name="Clorotekal FDA label" />

==Medical uses== Chloroprocaine (Nesacaine) is indicated for the production of local anesthesia by infiltration and peripheral nerve block;<ref name="Nesacaine FDA label" /> and for the production of local anesthesia by infiltration, peripheral and central nerve block, including lumbar and caudal epidural blocks.<ref name="Nesacaine FDA label" />

Chloroprocaine (Clorotekal) is indicated for intrathecal injection in adults for the production of subarachnoid block (spinal anesthesia).<ref name="Clorotekal FDA label" />

Chloroprocaine is used for regional anesthesia including spinal anesthesia, caudal anesthesia and epidural anesthesia.<ref>{{cite web |url=https://www.medicines.org.uk/emc/product/8805 |title=Ampres 10 mg/ml solution for injection |author=Sintetica Limited |date=9 March 2017 |publisher=EMC |access-date=2 December 2018 |archive-date=19 August 2019 |archive-url=https://web.archive.org/web/20190819153930/https://www.medicines.org.uk/emc/product/8805 |url-status=live }}</ref><ref name=PDR>{{cite web |url=https://m.pdr.net/Mobile/Pages/drug-summary/Nesacaine-chloroprocaine-hydrochloride-2745 |title=chloroprocaine hydrochloride |author=Physicians' Desk Reference |author-link=Physicians' Desk Reference |publisher=PDR.net |location=USA |access-date=2 December 2018 |archive-date=19 August 2019 |archive-url=https://web.archive.org/web/20190819153937/https://m.pdr.net/Mobile/Pages/drug-summary/Nesacaine-chloroprocaine-hydrochloride-2745 |url-status=live }}</ref>

It is also indicated for local anesthesia including brachial plexus block, cervical nerve block, occipital nerve block. mandibular nerve block or maxillary nerve block for dental anesthesia, ophthalmic anesthesia via infraorbital nerve block, ulnar nerve block, paravertebral block, intercostal nerve block, sciatic nerve block, stellate ganglion block, lumbar sympathetic block and interdigital block.<ref name=PDR/>

It is also used for obstetric anesthesia including pudendal nerve block and paracervical block.<ref name=PDR/>

Chloroprocaine (Iheezo) is indicated for ocular surface anesthesia.<ref name="Iheezo FDA label">{{cite web | title=Iheezo- chloroprocaine hydrochloride ophthalmic gel gel | website=DailyMed | date=27 September 2022 | url=https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ea3b2d2c-8b33-d199-e053-2995a90a699c | access-date=21 January 2023}}</ref>

==Subarachnoid block==

Chloroprocaine was developed to meet the need for a short-acting spinal anaesthetic that is reliable and has a favourable safety profile to support the growing need for day-case surgery. Licensed in Europe for surgical procedures up to 40 minutes, chloroprocaine is an ester-type local anaesthetic with the shortest duration of action of all the established local anaesthetics. It has a significantly shorter duration of action than lidocaine and is significantly less toxic. Chloroprocaine has a motor block lasting for 40 minutes, a rapid onset time of 3–5 minutes (9.6 min ± 7.3 min at 40 mg dose; 7.9 min ± 6.0 min at 50 mg dose) and a time to ambulation of 90 minutes without complications, especially lacking transient neurologic symptomatology.

These data are based upon a retrospective review of 672 patients suitable for spinal anesthesia in surgical procedures less than 60 minutes' duration using 30–40 mg chloroprocaine. The results showed good surgical anesthesia, a fast onset time, and postoperative mobilization after 90 minutes without complications.<ref>{{cite journal | title = Ampres (chloroprocaine) Summary of Product Characteristics | vauthors = Palas T | quote = Cloroprocaina in chirurgia ambulatoriale: uno studio osservazionale | journal = Perimed | date = 2009 | volume = 3 | issue = 2 | pages = 31–34 }}</ref>

The use of chloroprocaine in the subarachnoid space has been questioned.<ref>{{cite journal | vauthors = Drasner K | title = Chloroprocaine spinal anesthesia: back to the future? | journal = Anesthesia & Analgesia | date = February 2005 | volume = 100 | issue = 2 | pages = 549–52 | doi = 10.1213/01.ANE.0000143382.89888.C3 | pmid = 15673892 | doi-access = free }}</ref> In the early 1980s, several cases were reported of neurological deficits after inadvertent intrathecal injections intended for epidural delivery.<ref name="pmid7189987">{{cite journal | vauthors = Reisner LS, Hochman BN, Plumer MH | title = Persistent neurologic deficit and adhesive arachnoiditis following intrathecal 2-chloroprocaine injection | journal = Anesthesia and Analgesia | volume = 59 | issue = 6 | pages = 452–4 | date = June 1980 | doi = 10.1213/00000539-198006000-00014 | pmid = 7189987 }}</ref> These doses were an order of magnitude higher than is currently used for intrathecal delivery.<ref name="pmid21039353">{{cite journal | vauthors = Förster JG, Kallio H, Rosenberg PH, Harilainen A, Sandelin J, Pitkänen MT | title = Chloroprocaine vs. articaine as spinal anaesthetics for day-case knee arthroscopy | journal = Acta Anaesthesiologica Scandinavica | volume = 55 | issue = 3 | pages = 273–81 | date = March 2011 | pmid = 21039353 | doi = 10.1111/j.1399-6576.2010.02325.x | s2cid = 205430566 }}</ref><ref name="Förster_2013">{{cite journal | vauthors = Förster JG, Rosenberg PH, Harilainen A, Sandelin J, Pitkänen MT | title = Chloroprocaine 40 mg produces shorter spinal block than articaine 40 mg in day-case knee arthroscopy patients | journal = Acta Anaesthesiologica Scandinavica | volume = 57 | issue = 7 | pages = 911–9 | date = August 2013 | pmid = 23521140 | doi = 10.1111/aas.12107 | s2cid = 42930157 }}</ref><ref name="pmid21203878">{{cite journal | vauthors = Lacasse MA, Roy JD, Forget J, Vandenbroucke F, Seal RF, Beaulieu D, McCormack M, Massicotte L | title = Comparison of bupivacaine and 2-chloroprocaine for spinal anesthesia for outpatient surgery: a double-blind randomized trial | journal = Canadian Journal of Anaesthesia | volume = 58 | issue = 4 | pages = 384–91 | date = April 2011 | pmid = 21203878 | doi = 10.1007/s12630-010-9450-x | s2cid = 31870857 | doi-access = free }}</ref> It is also thought that these deficits were also related to the preservative sodium bisulfite,<ref>{{cite journal | vauthors = Gissen AJ, Datta S, Lambert D | title = The chloroprocaine controversy: II. Is chloroprocaine neurotoxic? | journal = Regional Anesthesia and Pain Medicine | date = July 1984 | volume = 9 | issue = 3 | pages = 135–45 | doi = 10.1136/rapm-00115550-198409030-00004 | doi-broken-date = 11 July 2025 |url=https://rapm.bmj.com/content/9/3/135 | doi-access = free }}</ref><ref name="pmid1443708">{{cite journal | vauthors = Wang BC, Li D, Hiller JM, Simon EJ, Budzilovich G, Hillman DE | title = Lumbar subarachnoid ethylenediaminetetraacetate induces hindlimb tetanic contractions in rats: prevention by CaCl2 pretreatment; observation of spinal nerve root degeneration | journal = Anesthesia and Analgesia | volume = 75 | issue = 6 | pages = 895–9 | date = December 1992 | pmid = 1443708 | doi = 10.1213/00000539-199212000-00006 | doi-access = free }}</ref> although this is also controversial.<ref name="pmid14695728">{{cite journal | vauthors = Taniguchi M, Bollen AW, Drasner K | title = Sodium bisulfite: scapegoat for chloroprocaine neurotoxicity? | journal = Anesthesiology | volume = 100 | issue = 1 | pages = 85–91 | date = January 2004 | pmid = 14695728 | doi = 10.1097/00000542-200401000-00016 | s2cid = 9604835 | doi-access = free }}</ref><ref name="pmid2346671">{{cite journal | vauthors = Cabré F, Marín C, Cascante M, Canela EI | title = Occurrence and comparison of sulfite oxidase activity in mammalian tissues | journal = Biochemical Medicine and Metabolic Biology | volume = 43 | issue = 2 | pages = 159–62 | date = April 1990 | pmid = 2346671 | doi = 10.1016/0885-4505(90)90021-r }}</ref>

Some studies have been published on the safe use of intrathecal chloroprocaine when appropriate dosage is used and with preservative-free preparations.<ref name="pmid23320599">{{cite journal | vauthors = Goldblum E, Atchabahian A | title = The use of 2-chloroprocaine for spinal anaesthesia | journal = Acta Anaesthesiologica Scandinavica | volume = 57 | issue = 5 | pages = 545–52 | date = May 2013 | pmid = 23320599 | doi = 10.1111/aas.12071 | s2cid = 525005 }}</ref><ref name="Förster_2013" />

It is approved for intrathecal use in the United States,<ref>{{cite web | title=Drug Approval Package: Clorotekal (chloroprocaine HCl) Injection | website=U.S. Food and Drug Administration (FDA) | date=21 March 2018 | url=https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208791Orig1s000TOC.cfm | access-date=27 December 2024}}</ref> Europe,<ref>{{cite web | title = Rediscovered Local Holds Promise for Spinal Anesthesia | url = http://www.anesthesiologynews.com/ViewArticle.aspx?d=Clinical+Anesthesiology&d_id=1&i=June+2013&i_id=962&a_id=23319 | work = Anesthesiology News | publisher = McMahon Publishing | date = 5 June 2013 | access-date = 20 September 2013 | archive-date = 29 September 2022 | archive-url = https://web.archive.org/web/20220929022630/https://www.anesthesiologynews.com/ViewArticle.aspx?d=Clinical+Anesthesiology&d_id=1&i=June+2013&i_id=962&a_id=23319 | url-status = live }}</ref> and Canada.<ref name="Clorotekal CA RDS" />

==Obstetrics==

Amide-linked local anesthetic agents, such as lidocaine and bupivacaine, can become "trapped" in their ionized forms on the fetal side of the placenta, so their net transfer across the placenta is increased. An ester-linked local anesthetic agent, such as 2-chloroprocaine, is rapidly metabolized, and placental transfer is limited. Since the metabolism of 2-chloroprocaine by fetal plasma is slower than in maternal plasma, the potential for ion trapping exists. Fetal pH is slightly lower than maternal (7.32 to 7.38), thus most unionized drugs are "ion trapped" to a degree, even in a healthy fetus. Chloroprocaine (pKa 8.7) is the drug of choice for epidural analgesia and a decompensating fetus, because it does not participate in ion trapping. Placental transfer of 2-chloroprocaine is not influenced by fetal acidosis.<ref name="pmid3970100">{{cite journal | vauthors = Philipson EH, Kuhnert BR, Syracuse CD | title = Fetal acidosis, 2-chloroprocaine, and epidural anesthesia for cesarean section | journal = American Journal of Obstetrics and Gynecology | volume = 151 | issue = 3 | pages = 322–4 | date = February 1985 | pmid = 3970100 | doi = 10.1016/0002-9378(85)90295-9 }}</ref>

The ''in vitro'' half-life of chloroprocaine is 21 seconds for maternal and 43 seconds for fetal blood. In patients who are homozygous atypical for plasma cholinesterase, chloroprocaine typically exists for two minutes in circulation.<ref>{{cite book | title = Obstetric Anesthesia: Principles and Practice | edition = 3rd | vauthors = Chestnut DH | location = Philadelphia | publisher = Elsevier Mosby | date = 2004 | page = 333 | isbn = 978-0-323-02357-3 }}</ref><ref>{{cite book | title = Shnider and Levinson's Anesthesia for Obstetrics | edition = 4th | veditors = Hughes SC, Levinson G, Rosen MA | location = Philadelphia | publisher = Lippincott Williams & Wilkins | date = 2002 | page = 75 | isbn = 978-0-683-30665-1 }}</ref>

==Synthesis== class=skin-invert-image|800px|center|thumb|Chloroprocaine synthesis: H.C. Marks, H.I. Rubin, {{US Patent|2460139}} (1949 to Wallace & Tiernan Inc). The hydrochloride salt of 4-amino-2-chlorobenzoyl chloride is made by the reaction of 2-chloro-4-aminobenzoic acid with thionyl chloride.<ref>{{cite book | vauthors = Vardanyan RS, Hruby VJ| chapter = Local anesthetics | date = January 2006 | title = Synthesis of Essential Drugs |pages=9–18 |place=Amsterdam |publisher=Elsevier |doi=10.1016/b978-044452166-8/50002-9 |isbn=978-0-444-52166-8 }}</ref> Synthesis of this drug is then accomplished by directly reacting the product of the last step with the hydrochloride salt of 2-diethylaminoethanol.<ref>{{Cite web |title=Preparation method of chloroprocaine hydrochloride |url=https://patents.google.com/patent/CN105968019A/en |website=Google Patents}}</ref>

==References== {{reflist}}

Category:Local anesthetics Category:4-Aminobenzoate esters Category:Chlorobenzene derivatives Category:Diethylamino compounds