Piperoxan hydrochloride(also known as Piperoxan HCl, or benodaine) is a novel, selective and potent α2 adrenoceptor antagonist. Moreover, it was the original antihistamine.

Physicochemical Properties

Molecular Formula	C14H20CLNO2
Molecular Weight	269.769
Exact Mass	269.118
Elemental Analysis	C, 62.33; H, 7.47; Cl, 13.14; N, 5.19; O, 11.86
CAS #	135-87-5
Related CAS #	59-39-2; 135-87-5 (HCl)
PubChem CID	101619
Appearance	Solid powder
Density	1.113g/cm3
Boiling Point	331.5ºC at 760mmHg
Flash Point	118.1ºC
Vapour Pressure	0.000155mmHg at 25°C
LogP	3.052
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	2
Heavy Atom Count	18
Complexity	240
Defined Atom Stereocenter Count	0
SMILES	[H]Cl.N1(CC2OC3=CC=CC=C3OC2)CCCCC1
InChi Key	BITRJBQGQMGGQI-UHFFFAOYSA-N
InChi Code	InChI=1S/C14H19NO2.ClH/c1-4-8-15(9-5-1)10-12-11-16-13-6-2-3-7-14(13)17-12;/h2-3,6-7,12H,1,4-5,8-11H2;1H
Chemical Name	1-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)piperidine;hydrochloride
Synonyms	F 933 hydrochloride; Piperoxan HCl; benodaine; Piperoxane hydrochloride; F933; F-933
HS Tariff Code	2934.99.9001
Storage	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.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

Targets	α2 adrenoceptor
ln Vitro	In the event that the medulla is superfused with α2 adrenoceptor antagonist Piperoxane (50 μM; 5 min) and the pons is filled with artificial cerebrospinal fluid (ACSF), three inactive preparations exhibit rhythmic phrenic bursts at a low frequency (2-4 c/min). Meanwhile, the phrenic burst frequency of the twelve active preparations increases significantly during the final 3 min of Piperoxane applications (163±12% of the preceding mean frequency). When the preparations are superfused with either ACSF (n = 8) or the α2 adrenoceptor antagonist Piperoxane (50 μM; PIP-ACSF; n = 5), the effects of NA applications (25 μM; 5 min) are compared. The frequency of phrenic bursts is greatly increased by applying NA, either by itself (NA-ACSF) or in combination with Piperoxane (PIP-ACSF+NA). But piperoxane potentiates a phrenic burst frequency increase by blocking medullary α2 adrenoceptors. In the fifth minute of NA applications, the phrenic burst frequency increased to 171±11% of the mean control value when ACSF is applied alone, and 234±21% of the mean control value when PIP-ACSF is applied in control condition[1].
Cell Assay	The brain stems and cervical spinal cords of the mouse neonates (P0-P3) are removed and placed ventral sides up in a 2 mL chamber superfused with artificial cerebrospinal fluid (ACSF) at 27±0.25°C (mean±SD), renewed at a rate of 2 mL/min. The mice are then given ether anesthesia and decerebrated. By bubbling carbogene (95% O2-5% CO2), the ACSF, which contains (in mM) 129 NaCl, 3.35 KCl, 1.26 CaCl2, 1.15 MgCl2, 21 NaHCO3, 0.58 NaH2PO4, and 30 glucose, is oxygenated and equilibrated (pH 7.4 at 27°C). In the pharmaceutical tests, this is swapped out for an additional ACSF containing bioreactive materials: either α2 adrenoceptor antagonists, such as piperoxane at 50 μM (PIP-ACSF) or yohimbine at 50 μM (YO-ACSF), or noradrenaline at 25 μM (NA-ACSF). In certain experiments, a solution of either ACSF or NA (1 mM) is pressure-expelled from the A5 nucleus after a patch-clamp microelectrode with a diameter of 1 μm is lowered into the ventral pons. For a two-second pressure pulse, the estimated ejected volume is 20 nL[1].
Animal Protocol	Mice: The mice used are male Balb-C mice that weigh 20–25 g. Only slightly opposes the antinociceptive effect of (-)-isoprenaline in mice pretreated with the α-adrenoceptor antagonist Piperoxan or naloxone, both at a dose of 3×10-5 mol /kg s.c. given 15 min before the acetic acid. The antagonists in question yield dose-ratios of 1.45 and 1.7.
References	[1]. Nasal trigeminal inputs release the A5 inhibition received by the respiratory rhythm generator of the mouse neonate. J Neurophysiol. 2004 Feb;91(2):746-58. [2]. The antinociceptive action of some beta-adrenoceptor agonists in mice. Br J Pharmacol. 1986 Jul;88(3):515-21.

Solubility Data

Solubility (In Vitro)	DMSO: ~54 mg/mL (~200.2 mM) Water: ~54 mg/mL Ethanol: ~40 mg/mL
Solubility (In Vivo)	Solubility in Formulation 1: 25 mg/mL (92.67 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.7069 mL	18.5343 mL	37.0686 mL
	5 mM	0.7414 mL	3.7069 mL	7.4137 mL
	10 mM	0.3707 mL	1.8534 mL	3.7069 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.