Cruzipain expression levels are not decreased or the parasite's total proteolytic activity is not inhibited when dibucaine (cinchaine) decreases the breakdown of BSA-gold complexes in depots [1]. Within two minutes, the quaternary ammonium compound dibucaine reversibly suppresses SChE to very low levels. Inhibition works incredibly well. For BuTch, the IC(50) is 5.3 microM, and for AcTch, it is 3.8 microM. When compared to AcTch, the inhibition constant is linear mixed (competitive/non-competitive), with inhibition constants K(i) and K(I) of 0.66 and 2.5 microM, respectively. In contrast, the inhibition is competitive when compared to BuTch, with K(i) being 1.3 microM. Dibucaine's butoxy side chain is longer than AcTch's ethylene group and resembles the butyl group of BuTch [2].

Absorption, Distribution and Excretion
In general, ionized forms (salts) of local anesthetics are not readily absorbed through intact skin. However, both nonionized (bases) and ionized forms of local anesthetics are readily absorbed through traumatized or abraded skin into the systemic circulation.
THE DRUG IS PARTIALLY METABOLIZED & A PORTION IS ELIMINATED UNCHANGED.
... RADIOACTIVE /SPINAL/ LOCAL ANESTHETICS ARE CONCN WITHIN SPINAL NERVE ROOTS AS WELL AS POSTERIOR & LATERAL COLUMNS OF SPINAL CORD. ... RATE OF ENZYMATIC HYDROLYSIS OF LOCAL ANESTHETIC AGENTS BY SPINAL FLUID IS SLOW. /LOCAL ANESTHETICS/
DURATION ... DEPENDS UPON RATE @ WHICH DRUG IS REMOVED FROM CEREBROSPINAL FLUID & FROM NERVE ROOTS WHERE IT EXERTS ITS ACTION. /LOCAL ANESTHETICS/
AT AUTOPSY, DIBUCAINE WAS DEMONSTRATED FROM UPPER SPINAL CORD (3.11 MUG/0.1 G), LOWER SPINAL CORD (7.15 MUG/0.1 G), LIVER (0.299 MUG/1.0 G) & KIDNEY (0.181 MUG/1.0 G).

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Metabolism / Metabolites
Primarily hepatic.
METABOLISM OF AMIDE-LINKED LOCAL ANESTHETICS IS MORE COMPLEX /THAN ESTER TYPES/ ...

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Topical dibucaine has not been studied during breastfeeding, but is unlikely to affect her breastfed infant if it is applied away from the breast. However, dibucaine ointment should not be applied to the nipple area, because ingestion by infants has caused seizures, arrhythmias, cardiovascular collapse and death after direct ingestion by toddlers.
◉ 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.

[1]. Souto-Padron, T., A.P. Lima, and O. Ribeiro Rde, Effects of dibucaine on the endocytic/exocytic pathways in Trypanosoma cruzi. Parasitol Res, 2006. 99(4): p. 317-20.

[2]. Elamin, B., Dibucaine inhibition of serum cholinesterase. J Biochem Mol Biol, 2003. 36(2): p. 149-53.

Cinchocaine is a monocarboxylic acid amide that is the 2-(diethylamino)ethyl amide of 2-butoxyquinoline-4-carboxylic acid. One of the most potent and toxic of the long-acting local anesthetics, its parenteral use was restricted to spinal anesthesia. It is now generally only used (usually as the hydrochloride) in creams and ointments and in suppositories for temporary relief of pain and itching associated with skin and anorectal conditions. It has a role as a topical anaesthetic. It is a monocarboxylic acid amide, a tertiary amino compound and an aromatic ether.
A local anesthetic of the amide type now generally used for surface anesthesia. It is one of the most potent and toxic of the long-acting local anesthetics and its parenteral use is restricted to spinal anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1006)
Dibucaine is a Standardized Chemical Allergen. The physiologic effect of dibucaine is by means of Increased Histamine Release, and Cell-mediated Immunity.
Dibucaine is a quinoline derivative and amino amide with anesthetic activity. Dibucaine reversibly binds to and inactivates sodium channels in the neuronal cell membrane. Inhibition of sodium channels prevents the depolarization of nerve cell membranes and inhibits subsequent propagation of impulses along the course of the nerve, thereby limiting the excitation of nerve endings. This results in loss of sensation.
A local anesthetic of the amide type now generally used for surface anesthesia. It is one of the most potent and toxic of the long-acting local anesthetics and its parenteral use is restricted to spinal anesthesia. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1006)
See also: Dibucaine Hydrochloride (has salt form); Dibucaine benzoate (is active moiety of); Dibucaine; lidocaine (component of).

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Drug Indication
For production of local or regional anesthesia by infiltration techniques such as percutaneous injection and intravenous regional anesthesia by peripheral nerve block techniques such as brachial plexus and intercostal and by central neural techniques such as lumbar and caudal epidural blocks.

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Mechanism of Action
Local anesthetics block both the initiation and conduction of nerve impulses by decreasing the neuronal membrane's permeability to sodium ions through sodium channel inhibition. This reversibly stabilizes the membrane and inhibits depolarization, resulting in the failure of a propagated action potential and subsequent conduction blockade.
... PREVENT THE GENERATION & THE CONDUCTION OF THE NERVE IMPULSE. THEIR PRIMARY SITE OF ACTION IS THE CELL MEMBRANE. ... BLOCK CONDUCTION BY DECREASING OR PREVENTING THE TRANSIENT INCREASE IN THE PERMEABILITY OF EXCITABLE MEMBRANES TO NA IONS THAT IS NORMALLY PRODUCED BY A SLIGHT DEPOLARIZATION ... /LOCAL ANESTHETICS/
AS ANESTHETIC ACTION PROGRESSIVELY DEVELOPS IN A NERVE, THE THRESHOLD FOR ELECTRICAL EXCITABILITY GRADUALLY INCREASES, THE RATE OF RISE OF THE ACTION POTENTIAL DECLINES, IMPULSE CONDUCTION SLOWS, & THE SAFETY FACTOR FOR CONDUCTION DECREASES; THESE FACTORS DECREASE PROBABILITY OF PROPAGATION OF THE ACTION POTENTIAL, AND NERVE CONDUCTION FAILS. /LOCAL ANESTHETICS/
... CAN BLOCK K ION CHANNELS. ... BLOCKADE OF CONDUCTION IS NOT ACCOMPANIED BY ANY LARGE OR CONSISTENT CHANGE IN RESTING MEMBRANE DUE TO BLOCK OF K ION CHANNELS. /LOCAL ANESTHETICS/
... SITE AT WHICH LOCAL ANESTHETICS ACT, AT LEAST IN THEIR CHARGED FORM, IS ACCESSIBLE ONLY FROM THE INNER SURFACE OF THE MEMBRANE. ... LOCAL ANESTHETICS APPLIED EXTERNALLY FIRST MUST CROSS THE MEMBRANE BEFORE THEY CAN EXERT A BLOCKING ACTION. /LOCAL ANESTHETICS/
... ACT ON ANY PART OF NERVOUS SYSTEM & ON EVERY TYPE OF NERVE FIBER. /LOCAL ANESTHETICS/

C20H29N3O2

343.463165044785

343.225

85-79-0

Dibucaine hydrochloride;61-12-1

3025

White to yellow solid powder

99-101 °C (HCl salt)
64 °C
Melting point: 62-65 °C
99 - 101 °C (hydrochloride salt)

4.4

1

4

10

25

387

0

O=C(C1C2C(=CC=CC=2)N=C(OCCCC)C=1)NCCN(CC)CC

PUFQVTATUTYEAL-UHFFFAOYSA-N

InChI=1S/C20H29N3O2/c1-4-7-14-25-19-15-17(16-10-8-9-11-18(16)22-19)20(24)21-12-13-23(5-2)6-3/h8-11,15H,4-7,12-14H2,1-3H3,(H,21,24) SMILES

2-butoxy-N-[2-(diethylamino)ethyl]quinoline-4-carboxamide

Dibucaine Cinchocaine Nupercainal Nupercaine Sovcaine Dibucaine Base

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 (~291.15 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.28 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 (7.28 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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 (Please use freshly prepared in vivo formulations for optimal results.)