In N2A cells, diphenidol (0.1-100 µM) inhibits Na+ current with an IC50 of 0.77 µM and a Hill coefficient of 1.15 [1].

In rats, dofetidol (0.77 mg/rat; intrathecal injection; single dose) inhibits proprioception, nociception, and motor performance [1]. Rats with CCI-induced mechanical allodynia can be successfully reversed or entirely blocked by difenidol (0.62, 3.09 mg/kg; intraperitoneal injection; once daily for 7 days) [2].

Animal/Disease Models: Male Spraguee Dawley rat (275-325 g) [1].
Doses: 0.77 mg/rat (2.50 µmol/rat)
Route of Administration: Intrathecal injection; single.
Experimental Results: Resulting in 100% obstruction of motor function, proprioception and nociception, with durations of approximately 51 minutes, 77 minutes and 123 minutes respectively.

---

Animal/Disease Models: Male adult SD (SD (Sprague-Dawley)) rat (200-250 g; CCI rat model) [2].
Doses: 0.62, 3.09 mg/kg (2, 10 µmol/kg)
Route of Administration: intraperitoneal (ip) injection; single dose daily for 7 days.
Experimental Results: Blockade of CCI-induced low mechanical withdrawal threshold 1 hour after administration. Reduces TNF-α levels on day 7 and alleviates neuropathic tactile allodynia after CCI in rats.

Absorption, Distribution and Excretion
After oral administration, it is well absorbed via the gastrointestinal tract. Metabolisms/Metabolites In dogs and humans, the major urinary metabolite of benzoyldiphenyl ether is N-(4,4-diphenyl-4-hydroxybutyl)-δ-aminovaleric acid (not less than 50% of the dose). Secondary urinary metabolites include a phenolic compound and a lactam compound. Biological Half-Life 4 hours

Non-Human Toxicity Values
Mice oral LD50: 430 mg/kg/hydrochloride/
Mice intraperitoneal LD50: 105 mg/kg/hydrochloride/
Mice intravenous LD50: 37 mg/kg/hydrochloride/
Rat oral LD50: 515 mg/kg/hydrochloride/
For more complete non-human toxicity data for dibenzoneols (6 in total), please visit the HSDB record page.

[1]. Inhibition of voltage-gated K+ channels and Ca2+ channels by diphenidol. Pharmacol Rep. 2012;64(3):739-44.

[2]. Diphenidol inhibited sodium currents and produced spinal anesthesia. Neuropharmacology. 2010 Jun;58(7):1147-52.

[3]. Diphenidol inhibited sodium currents and produced spinal anesthesia. Neuropharmacology. 2010 Jun;58(7):1147-52.

[4]. Systemic diphenidol reduces neuropathic allodynia and TNF-alpha overexpression in rats after chronic constriction injury. Neurosci Lett. 2013 Sep 27;552:62-5.

[5]. Neuropharmacological mechanisms of emesis. I. Effects of antiemetic drugs on motion- and apomorphine-induced pica in rats. Methods Find Exp Clin Pharmacol. 1995 Nov;17(9):589-90.

Diphenidol is a tertiary alcohol, formed by replacing two phenyl groups at the 1-position of butan-1-ol and one piperidin-1-yl group at the 4-position. It is an antiemetic. It belongs to the piperidine class, tertiary alcohol class, and benzene class. Diphenidol is an antiemetic used to treat vomiting and dizziness. Overdose of Diphenidol in children may lead to serious poisoning. Diphenidol is an antiemetic. The physiological action of Diphenidol is through the suppression of vomiting. Drug Indications Used for the prevention and treatment of peripheral (labyrinthine) vertigo, as well as nausea and vomiting caused by Meniere's disease and middle or inner ear surgery. It can also be used to control nausea and vomiting caused by surgery, malignant tumors, labyrinthine dysfunction, antitumor drug therapy, radiation sickness, and infectious diseases. FDA Label Mechanism of Action The mechanism by which Diphenidol exerts its antiemetic and antivertigo effects is not fully understood. It is believed to reduce vestibular stimulation, inhibit labyrinthine function, and have anticholinergic effects. Its effect on the medullary chemoreceptor trigger zone may also contribute to its antiemetic effect. Diphenidol has no significant sedative, tranquilizing, or antihistamine effects. It has a weak peripheral anticholinergic effect.
Experiments have shown that it has a weak parasympathetic blocking effect, but lacks significant sedative, tranquilizing, or antihistamine properties.
.../Diphenidol/is believed to act on the vestibular organs of the ear...

---

Therapeutic Uses
Anemetic; Histamine H1 receptor antagonist
...An antiemetic that can be taken orally, rectally, intramuscularly, or intravenously, used to treat nausea and vomiting caused by infectious diseases, malignant tumors, radiation sickness, general anesthesia, and antitumor drug treatment. ...It can also be used to treat vestibular vertigo.
In adults, this drug is also effective for...labyrinthitis after middle and inner ear surgery and Meniere's disease. Its efficacy in treating vertigo in children has not been studied. /HCL/

---

Drug Warnings
Because Diphenidol has a parasympathetic blocking effect, it should be used with caution in patients with glaucoma, benign prostatic hyperplasia, peptic ulcers, pyloric or duodenal obstruction, or cardiac spasm.
...It is not recommended for use during pregnancy-related nausea and vomiting, as its safety in this condition has not been established.

---

Pharmacodynamics
Diphenidol is used to control nausea and vomiting. It has an anti-vertigo effect on the vestibular system, controlling nausea and vomiting by inhibiting chemoreceptor trigger zones, thereby preventing motion sickness.

C21H27NO

309.4452

309.209

972-02-1

Diphenadol-d10

3055

NEEDLES FROM PETROLEUM ETHER
WHITE CRYSTALLINE POWDER

1.066 g/cm3

473.3ºC at 760 mmHg

105ºC

233.5ºC

1.5614 (estimate)

4.126

1

2

6

23

307

0

C1(C(C2C=CC=CC=2)(O)CCCN2CCCCC2)C=CC=CC=1

OGAKLTJNUQRZJU-UHFFFAOYSA-N

InChI=1S/C21H27NO/c23-21(19-11-4-1-5-12-19,20-13-6-2-7-14-20)15-10-18-22-16-8-3-9-17-22/h1-2,4-7,11-14,23H,3,8-10,15-18H2

1,1-diphenyl-4-piperidin-1-ylbutan-1-ol

SKF478 SKF-478 SKF 478

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)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

---

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

View More

Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

---

Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

View More

Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

---

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

---

 (Please use freshly prepared in vivo formulations for optimal results.)