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.

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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
Well absorbed from gastrointestinal tract following oral administration.

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Metabolism / Metabolites
IN DOGS & IN MAN, PRINCIPAL URINARY METABOLITE OF DIPHENIDOL...WAS N-(4,4-DIPHENYL-4-HYDROXYBUTYL)-DELTA-AMINOVALERIC ACID...(NOT LESS THAN 50% OF DOSE)... MINOR URINARY METABOLITES INCL A PHENOL...& A LACTAM...

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Biological Half-Life
4 hours

Non-Human Toxicity Values
LD50 MICE ORAL 430 MG/KG /HCL/
LD50 MICE INTRAPERITONEAL 105 MG/KG /HCL/
LD50 MICE INTRAVENOUS 37 MG/KG /HCL/
LD50 RATS ORAL 515 MG/KG /HCL/
For more Non-Human Toxicity Values (Complete) data for DIPHENIDOL (6 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 that is butan-1-ol substituted by two phenyl groups at position 1 and a piperidin-1-yl group at position 4. It has a role as an antiemetic. It is a member of piperidines, a tertiary alcohol and a member of benzenes.
Diphenidol is an antiemetic agent used in the treatment of vomiting and vertigo. Diphenidol overdose may result in serious toxicity in children.
Diphenidol is an Antiemetic. The physiologic effect of diphenidol is by means of Emesis Suppression.

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Drug Indication
For use in the prevention and symptomatic treatment of peripheral (labyrinthine) vertigo and associated nausea and vomiting that occur in such conditions as Meniere's disease and surgery of the middle and inner ear. Also for the control of nausea and vomiting associated with postoperative states, malignant neoplasms, labyrinthine disturbances, antineoplastic agent therapy, radiation sickness, and infectious diseases.
FDA Label

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Mechanism of Action
The mechanism by which diphenidol exerts its antiemetic and antivertigo effects is not precisely known. It is thought to diminish vestibular stimulation and depress labyrinthine function and as an antimuscarinic agent. An action on the medullary chemoreceptive trigger zone may also be involved in the antiemetic effect. Diphenidol has no significant sedative, tranquilizing, or antihistaminic action. It has a weak peripheral anticholinergic effect.
EXPTL, IT HAS BEEN SHOWN TO EXHIBIT WEAK PARASYMPATHOLYTIC ACTIONS, BUT TO LACK SIGNIFICANT SEDATIVE, TRANQUILIZING, OR ANTIHISTAMINIC PROPERTIES.
.../DIPHENIDOL/ IS THOUGHT TO ACT UPON AURAL VESTIBULAR APPARATUS...

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Therapeutic Uses
Antiemetics; Histamine H1 Antagonists
...ANTIEMETIC AGENT FOR ORAL, RECTAL, IM, OR IV ADMIN, USEFUL IN MGMNT OF NAUSEA & VOMITING ASSOC WITH INFECTIOUS DISEASES, MALIGNANCIES, RADIATION SICKNESS, GENERAL ANESTHESIA, TREATMENT WITH ANTINEOPLASTIC AGENTS. ...ALSO USEFUL IN TREATMENT OF VERTIGO OF VESTIBULAR ORIGIN.
IN ADULTS, THIS DRUG ALSO IS EFFECTIVE IN...LABYRINTHITIS FOLLOWING SURGERY OF MIDDLE & INNER EAR, & MENIERE'S DISEASE. ITS USE IN TREATMENT OF VERTIGO IN CHILDREN HAS NOT BEEN INVESTIGATED. /HCL/

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Drug Warnings
SINCE DIPHENIDOL DOES POSSESS PARASYMPATHOLYTIC PROPERITES, IT SHOULD BE USED CAUTIOUSLY IN PT WITH GLAUCOMA, PROSTATIC HYPERTROPHY, PEPTIC ULCER, PYLORIC OR DUODENAL OBSTRUCTION, OR CARDIOSPASM.
...IT IS NOT RECOMMENDED FOR USE IN NAUSEA & VOMITING OF PREGNANCY, SINCE ITS SAFE USE IN THIS CONDITION HAS NOT BEEN ESTABLISHED.

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Pharmacodynamics
Diphenidol is used for control of nausea and vomiting. It has an antivertigo effect on the vestibular apparatus, inhibiting the chemoreceptor trigger zone to control nausea and vomiting, thus 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.

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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).

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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)

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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).

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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

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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.

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