Piperoxan hydrochloride

Piperoxan hydrochloride is an α2 adrenoceptor antagonist.

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Research Areas >> Inflammation/Immunology

adrenoceptor[1]

When the medulla is superfused with α2 adrenoceptor antagonist Piperoxane (50 μM; 5 min) while the pons is with artificial cerebrospinal fluid (ACSF), the three inactive preparations display rhythmic phrenic bursts at a low frequency (2-4 c/min), and the phrenic burst frequency of the 12 active ones significantly increases during the last 3 min of Piperoxane applications (163±12% of the previous mean frequency). In active medullary preparations, the effects of NA applications (25 μM; 5 min) are compared when the preparations sre superfused either by ACSF (n=8) or by the α2 adrenoceptor antagonist Piperoxane (50 μM; PIP-ACSF; n=5). NA applications either alone (NA-ACSF) or with Piperoxane (PIP-ACSF+NA) significantly increases the phrenic burst frequency. However, the blockage of the medullary α2 adrenoceptors by Piperoxane potentiates a phrenic burst frequency increase: during the fifth minute of NA applications, the phrenic burst frequency reached 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].

The mouse neonates (P0-P3) are ether-anesthetized and decerebrated; the brain stems and the cervical spinal cords are dissected out 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 ACSF [containing (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) by bubbling carbogene (95% O2-5% CO2). In the pharmacological experiments, this is replaced by another ACSF in which bioreactive substances are dissolved: noradrenaline at 25 μM (NA-ACSF) or α2 adrenoceptor antagonists, either Piperoxane at 50 μM (PIP-ACSF) or yohimbine at 50 μM (YO-ACSF). In some of the experiments, a patch-clamp microelectrode (1 μm diameter tip) is lowered within the ventral pons into the A5 nucleus where a solution of either ACSF or NA (1 mM) is pressure-ejected. The ejected volume is estimated 20 nL for a pressure pulse lasting 2 s[1].

Mice[2] Male Balb-C mice are used, weighing between 20 and 25 g. In mice pretreated with the α-adrenoceptor antagonist Piperoxan, or with naloxone, both at a dose of 3×10-5 mol /kg s.c. given 15 min before the acetic acid, the antinociceptive action of (-)-isoprenaline is only slightly antagonized. Dose-ratios of 1.45 and 1.7, are produced by these two antagonists.

[1]. Viemari JC, et al. 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]. Bentley GA, et al. The antinociceptive action of some beta-adrenoceptor agonists in mice. Br J Pharmacol. 1986 Jul;88(3):515-21.

Isoprenaline hydrochloride | ICI 118,551 (hydrochloride) | Phenylephrine hydrochloride | Yohimbine hydrochloride | Adrenaline | Ivabradine hydrochloride | Prazosin hydrochloride | Clenbuterol hydrochloride | Phentolamine mesilate | guanfacine hydrochloride | pimozide | Sotalol hydrochloride | Carvedilol | Atenolol | Metroprolol succinate

MOLECULAR FORMULA :

C14-H19-N-O2.Cl-H

MOLECULAR WEIGHT :

269.80

WISWESSER LINE NOTATION :

T66 BO EOT&J C1- AT6NTJ &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

502 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - excitement

REFERENCE :

JAPMA8 Journal of the American Pharmaceutical Association, Scientific Edition. (Washington, DC) V.29-49, 1940-60. For publisher information, see JPMSAE. Volume(issue)/page/year: 48,409,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

175 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - excitement

REFERENCE :

JAPMA8 Journal of the American Pharmaceutical Association, Scientific Edition. (Washington, DC) V.29-49, 1940-60. For publisher information, see JPMSAE. Volume(issue)/page/year: 48,409,1959

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

500 mg/kg

TOXIC EFFECTS :

Behavioral - analgesia

REFERENCE :

THERAP Therapie. (Doin, Editeurs, 8, Place de l'Odeon, F-75006 Paris, France) V.1- 1946- Volume(issue)/page/year: 13,17,1958

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

26 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

AIPTAK Archives Internationales de Pharmacodynamie et de Therapie. (Heymans Institute of Pharmacology, De Pintelaan 185, B-9000 Ghent, Belgium) V.4- 1898- Volume(issue)/page/year: 105,221,1956 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

735 mg/kg

SEX/DURATION :

female 3-9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :

PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 100,555,1959

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

250 mg/kg

SEX/DURATION :

female 5 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

REFERENCE :

PSEBAA Proceedings of the Society for Experimental Biology and Medicine. (Academic Press, Inc., 1 E. First St., Duluth, MN 55802) V.1- 1903/04- Volume(issue)/page/year: 100,555,1959