Within 4 minutes in PC12 cells, butamben (500 μM) inhibits 90% of control barium currents [2]. Fast but not slow Na+ channel inactivation is increased by butamben (100 μM; 2–10 minutes) [3].

In the mouse radiant heat tail flick test, butamben (0.5–50 mM; distal tail immersion for 2 minutes) exhibits dose-dependent analgesic efficacy in the form of a S [4].

Absorption, Distribution and Excretion
When butamben is administered epidurally in a suspension form, the physical characteristics of butamben allow a very slow release. When administered topically, butamben is also reported to have a very low systemic absorption which allows for a longer duration of action.
The metabolites found in plasma after cholinesterase processing are disposed of in the urine.
This pharmacokinetic property has not been determined.
Clearance is flow-limited and it highly depends on the state of protein-bound form.

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Metabolism / Metabolites
The metabolic pathway of butamben follows the same pattern of other local anesthetics and it is driven mainly by the hydrolysis via cholinesterase for the formation of inert metabolites.

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Biological Half-Life
The effective half-life of unencapsulated butamben is registered to be of 90 minutes. Some efforts were made to prepare D, L-lactic acid capsules which increased the half-life of butamben to even 400 hours.

Protein Binding
As all other local anesthetics, it is thought that butamben will be highly bound to plasma proteins, mainly to alpha-1-acid glycoprotein.

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Interactions
These agents /cholinesterase inhibitors such as antimyasthenics; cyclophosphamide; demecarium; echothiophate; neurotoxic insecticides, possibly including large quantities of topical malathion; isoflurophate; thiotepa/ may inhibit metabolism of ester derivatives; absorption of significant quantities of ester derivatives in patients receiving a cholinesterase inhibitor may lead to increased risk of toxicity. /Topical anesthetics/
Metabolites of PABA-derivative topical anesthetics may antagonize antibacterial activity of sulfonamides, especially if the anesthetics are absorbed in significant quantities over prolonged periods of time. /Topical anesthetics/

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Non-Human Toxicity Values
LD50 Mouse ip 67 mg/kg

[1]. Liposomal butamben gel formulations: toxicity assays and topical anesthesia in an animal model. J Liposome Res. 2017 Mar;27(1):74-82.

[2]. The local anesthetic butamben inhibits total and L-type barium currents in PC12 cells. Anesth Analg. 2008 Jun;106(6):1778-83.

[3]. The local anesthetic n-butyl-p-aminobenzoate selectively affects inactivation of fast sodium currents in cultured rat sensory neurons. Anesthesiology. 1995 Jun;82(6):1463-73.

[4]. Analgesic synergy between topical morphine and butamben in mice. Anesth Analg. 2003 Oct;97(4):1103-7, table of contents.

N-butyl-p-aminobenzoate is a yellow powder. Insoluble in water. (NTP, 1992)
Butamben is an amino acid ester resulting from the formal condensation of the carboxy group of 4-aminobenzoic acid with the hydroxy group of butan-1-ol. Its local anaesthetic properties have been used for surface anaesthesia of the skin and mucous membranes, and for relief of pain and itching associated with some anorectal disorders. It has a role as a local anaesthetic. It is a benzoate ester, a substituted aniline, an amino acid ester and a primary amino compound. It is functionally related to a 4-aminobenzoic acid and a butan-1-ol. It is a conjugate base of a butamben(1+).
Butamben is a local anesthetic in the form of n-butyl-p-aminobenzoate. Its structure corresponds to the standard molecule of a hydrophilic and hydrophobic domain separated by an intermediate ester found in most of the local anesthetics. Due to its very low water solubility, butamben is considered to be suitable only for topical anesthesia. The FDA removed all parenteral butamben products from the market, possibly due to the poor solubility of this drug.

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Drug Indication
Butamben was indicated for the treatment of chronic pain due to its long-duration effect. It is also indicated as a surface anesthetic for skin a mucous membrane and for the relief of pain and pruritus associated with anorectal disorders.

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Mechanism of Action
Butamben acts by inhibiting the voltage-gated calcium channels in dorsal root ganglion neurons. The modification in this channels is thought to cause a disturbance of the channel kinetics acceleration. It is reported as well that butamben is an inhibitor of the sodium channels and a delayed rectifier of potassium currents. All the effects of butamben are performed in the root ganglion neurons which suggests that the related anesthetic effect may be caused by the reduced electrical excitability.
...ACTION IS TO INTERFERE WITH INITIATION & TRANSMISSION OF NERVE IMPULSE. PRESENT THEORY HOLDS THAT LOCAL ANESTHETICS PREVENT DEPOLARIZATION OF NERVE MEMBRANE &, HENCE, PROPAGATION OF IMPULSE. ...THOUGHT TO BE DUE TO INTERFERENCE WITH MUTUAL EXCHANGE OF SODIUM & POTASSIUM IONS ACROSS MEMBRANE. /LOCAL ANESTHETICS/

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Therapeutic Uses
Anesthetics, Local
... POORLY SOL IN WATER &, CONSEQUENTLY, TOO SLOWLY ABSORBED TO BE TOXIC. THEY CAN BE APPLIED DIRECTLY TO WOUNDS & ULCERATED SURFACES WHERE THEY REMAIN LOCALIZED FOR LONG PERIODS OF TIME ... ACCOUNTS FOR SUSTAINED ANESTHETIC ACTION. ... MOST IMPORTANT MEMBERS OF SERIES ARE ... BUTAMBEN, USP (BUTYL AMINOBENZOATE, BUTESIN).
MEDICATION (VET): TOPICALLY, AS SPRAY OR IN OINTMENTS (1-2%). ...PARENTERAL USE IN OIL HAS PROVIDED ANESTHESIA FOR UP TO 1 OR 2 DAYS & IS OCCASIONALLY USED IN DEEP PERIANAL INJECTIONS (OR WITH PROCAINE BASE & BENZYL ALC) WHERE PROLONGED PROTECTION AGAINST STRAINING IS DESIRED.
Topical anesthetics are indicated to relieve pain, pruritus, and inflammation associated with minor skin disorders, including: burns, minor, including sunburn; bites (or stings), insect; dermatitis, contact, including poison ivy, poison oak, or poison sumac; wounds, minor such as cuts and scratches. /Included in US product labeling; Topical anesthetics/

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Pharmacodynamics
Butamben has been shown to selectively inhibit dorsal root pain signal transmission for periods of months when administered as epidural suspensions. The effect of butamben is not related to any significant loss of motor function which indicates that it targets specifically the pain-sensing C fibers of the dorsal root. When administered topically, butamben produced anesthesia by accumulating in the nerve cell membrane causing it to expand and lose its ability to depolarize and blocking the impulse transmission.

193.11

94-25-7

Butamben-d9

2482

White to off-white solid powder

1.1±0.1 g/cm3

325.7±0.0 °C at 760 mmHg

57-58 °C(lit.)

184.6±17.9 °C

0.0±0.7 mmHg at 25°C

1.540

3.01

1

3

5

14

174

0

O=C(C1C=CC(N)=CC=1)OCCCC

IUWVALYLNVXWKX-UHFFFAOYSA-N

InChI=1S/C11H15NO2/c1-2-3-8-14-11(13)9-4-6-10(12)7-5-9/h4-7H,2-3,8,12H2,1H3

butyl 4-aminobenzoate

PlanoformScuroformButambenButesinZyljectinNSC128464ButanylcaineButoformNSC 128464NSC-128464

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 (~517.49 mM)
H2O : ~0.1 mg/mL (~0.52 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (12.94 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 (12.94 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 (12.94 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.)