In TE671/RD cells, adiphenine (10 nM-1 mM; 3 minutes) inhibits α1*-nAChR function in a dose-dependent manner with an IC50 of 1.9 µM [1]. In SH-SY5Y cells, adiphenine (10 nM-1 mM; 3 minutes) inhibits α3α4*-nAChR function in a dose-dependent manner with an IC50 of 1.8 µM [1]. With an IC50 of 3.7 and 6.3 µM, respectively, adiphenine (10 nM-1 mM; 3 min) dose-dependently inhibits the function of α4β2- and α4β4-nAChR in SH-EP1 cells [1]. In HEK 293 cells, adiphenine (50–200 µM; 30–60 s) lowers the frequency of acetylcholine-induced single-channel currents [2].

In mice, adiphenine (ip) has an ED50 of 62 mg/kg and inhibits the hindleg tonic extensor component of maximal electroshock seizures (MES) [3].

Absorption, Distribution and Excretion
This study describes the behavior of a dual labelled drug, adiphenine, in the rat brain. Macroautoradiographies show images of the brain at different times after injection. Some of the tissue metabolites are identified at the brain level and the passage of the blood brain barrier is compared with tritiated water. The obtained data give very interesting indications on the blood brain distribution and on the metabolism at the brain level. Different techniques of high pressure liquid chromatography, macro- and histoautoradiographies allowed /visualization of/ how the drug is fixed on cerebral structures, giving indications on its mechanism of action.
The disposition of adiphenine labelled with 14C in two positions has been investigated in rats and mice after iv administration, and has been compared with that of the [14C]diethylethanolamine HCl and of the [14C]diphenylacetic acid. Radioactivity in the blood declined in a biphasic manner. Biliary elimination depended upon the 14C-labelled compound administered: less than 5% dose for the diethylethanolamine moiety, 100% dose for the carboxylic moiety. Of the radioactivity appearing in rat bile, less than 1% is associated with unchanged adiphenine. ... Uptake by the brain of [14C]adiphenine shortly after dosing is 15 times greater than that of blood. Radioactivity is also found in the hypophysis, the adrenals and melanoid pigments, with a concentration up to 30 times greater than that found in the blood.

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Metabolism / Metabolites
Major metabolites isolated from rat urine after administration of a single dose of (14C)adiphenine or (3H)adiphenine were identified by chromatography and n.m.r. spectrometry, and by comparison with authentic reference compounds chemically synthesized. Adiphenine was extensively metabolized by hydrolysis of the ester bond into diethylaminoethanol, diphenylacetic acid, diphenylacetic acid glucuronide and, in small quantities, the corresponding glycine and glutamine conjugates.
The disposition of adiphenine labelled with 14C in two positions has been investigated in rats and mice after iv administration ... In preliminary metabolic studies, three major metabolites have been identified: diphenylacetic acid, diethylethanolamine and a diphenylacetic acid glucuronide.

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Biological Half-Life
Adiphenine was administered in 3H-labelled form in doses of 15 mumole/kg intravenously to male Wistar rats. Plasma and brain levels of the unchanged drug were measured. The elimination of the 3H-labelled compound from the plasma was monophasic with a half-life of 13 minutes. The unchanged drug was detectable in the plasma for 30 minutes after the injection. The time course of brain levels of unchanged drug paralleled that found in the plasma with a half-life of 9 to 12 minutes. In all experiments, brain and plasma levels of unchanged adiphenine correlate highly.

Interactions
ALTHOUGH THE DRUG IS RELATIVELY NONTOXIC, IT SHOULD NOT BE USED IN CLOSE SEQUENCE WITH MORPHINE; THE COMBINATION APPEARS TO CAUSE APPREHENSION & TACHYCARDIA. /ADIPHENINE HYDROCHLORIDE/
Spasmolytin (adiphenine hydrochloride) and tropicine were administered im to albino rats poisoned with anabasine sulfate doses of 346, 519, and 692 mg/kg administered through gastric tube. The LD50 of anabasine sulfate, determined for treatment with adiphenine hydrochloride, was 570 mg/kg, and 403 mg/kg for treatment with tropacine. The LD16 and LD84 values determined for treatment with adiphenine hydrochloride and tropacine were 460 and 712 mg/kg and 288 and 498 mg/kg, respectively. Adiphenine hydrochloride and tropacine, administered im in 20 mg/kg doses, reduced the LD50 of anabasine sulfate by 271% and 191%, respectively./Adiphenine hydrochloride/

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Non-Human Toxicity Values
LD50 rat intravenous 27 mg/kg
LD50 mouse oral 600 mg/kg
LD50 mouse subcutaneous 400 mg/kg
LD50 mouse intravenous 21.5 mg/kg
For more Non-Human Toxicity Values (Complete) data for ADIPHENINE (6 total), please visit the HSDB record page.

[1]. Local anesthetics noncompetitively inhibit function of four distinct nicotinic acetylcholine receptor subtypes. J Pharmacol Exp Ther. 2001 Dec;299(3):1038-48.

[2]. The local anaesthetics proadifen and adiphenine inhibit nicotinic receptors by different molecular mechanisms. Br J Pharmacol, 2009. 157(5): p. 804-17.

[3]. Anticonvulsant properties of procaine, cocaine, adiphenine and related structures. Proc Soc Exp Biol Med. 1955 Oct;90(1):192-5.

[4]. Adiphenine plasma levels and blood-brain barrier crossing in the rat. Eur J Drug Metab Pharmacokinet, 1985. 10(4): p. 273-8.

2,2-diphenylacetic acid 2-(diethylamino)ethyl ester is a diarylmethane.

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Therapeutic Uses
Parasympatholytics
MEDICATION (VET): AS A SMOOTH MUSCLE RELAXANT IN URINARY OR GASTROINTESTINAL SPASMS.
ADIPHENINE HAS BEEN EMPLOYED FOR SYMPTOMATIC RELIEF OF GI DISORDERS CHARACTERIZED BY SPASM; FOR SPASTIC CONDITIONS OF THE GALL BLADDER & BILIARY DUCTS; FOR DYSMENORRHEA; FOR URETERAL COLIC; & FOR NEUROGENIC BLADDER & CERTAIN OTHER TYPES OF DYSURIA. /ADIPHENINE HYDROCHLORIDE/
.../IT/ DECR SPASM OF GI TRACT, BILIARY TRACT, URETER, & UTERUS WITHOUT PRODUCING CHARACTERISTIC ATROPINE EFFECTS ON SALIVARY, SWEAT, GI GLANDS, EYE, OR CARDIOVASCULAR SYSTEM, EXCEPT IN LARGE DOSES. /ADIPHENINE HYDROCHLORIDE/
For more Therapeutic Uses (Complete) data for ADIPHENINE (10 total), please visit the HSDB record page.

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Drug Warnings
ALTHOUGH THE DRUG IS RELATIVELY NONTOXIC, IT SHOULD NOT BE USED IN CLOSE SEQUENCE WITH MORPHINE; THE COMBINATION APPEARS TO CAUSE APPREHENSION & TACHYCARDIA. /ADIPHENINE HYDROCHLORIDE/

347.165

50-42-0

2031

White to off-white solid powder

423ºC at 760 mmHg

71-74 °C(lit.)

133.2ºC

4.505

0

3

9

23

311

0

Cl[H].O(C(C([H])(C1C([H])=C([H])C([H])=C([H])C=1[H])C1C([H])=C([H])C([H])=C([H])C=1[H])=O)C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])[H]

JGOAIQNSOGZNBX-UHFFFAOYSA-N

InChI=1S/C20H25NO2/c1-3-21(4-2)15-16-23-20(22)19(17-11-7-5-8-12-17)18-13-9-6-10-14-18/h5-14,19H,3-4,15-16H2,1-2H3

2-(diethylamino)ethyl 2,2-diphenylacetate

Adiphenine hydrochloride NSC-129224 NSC 129224

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

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 (~287.46 mM)
H2O : ≥ 50 mg/mL (~143.73 mM)

Solubility in Formulation 1: ≥ 3.25 mg/mL (9.34 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 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: ≥ 3.25 mg/mL (9.34 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 32.5 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: ≥ 3.25 mg/mL (9.34 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 32.5 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.)