Doxapram

Doxapram inhibits TASK-1, TASK-3, TASK-1/TASK-3 heterodimeric channel function with EC50 of 410 nM, 37 μM, 9 μM, respectively.Target: Potassium ChannelDoxapram is a respiratory stimulant. Doxapram (15-150 microM) also evoked 3H overflow in a concentration dependent manner, and doxapram-evoked release was inhibited by the Ca2+ channel blocker nifedipine (5 microM). Analysis of released tritiated compounds suggested that doxapram preferentially stimulated the release of dopamine. Our results indicate that the mechanism of action of doxapram shares similarities with that of hypoxia in the carotid body [1]. Doxapram (1-100 microM) caused rapid, reversible and dose-dependent inhibitions of K+ currents recorded in type I cells (IC50 approximately 13 microM). doxapram was also seen to directly inhibit Ca(2+)-independent K+ currents. Doxapram was a more potent inhibitor of the Ca(2+)-activated K+ currents recorded under control conditions. Doxapram (10 microM) was without effect on L-type Ca2+ channel currents recorded under conditions where K+ channel activity was minimized and was also without significant effect on K+ currents recorded in the neuronal cell line NG-108 15, suggesting a selective effect on carotid body type I cells. The effects of doxapram on type I cells show similarities to those of the physiological stimuli of the carotid body, suggesting that doxapram may share a similar mechanism of action in stimulating the intact organ [2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Neurological Disease

[1]. Cotten JF, et al. The ventilatory stimulant doxapram inhibits TASK tandem pore (K2P) potassium channel function but does not affect minimum alveolar anesthetic concentration. Anesth Analg, 2006, 102(3), 779-785.

[2]. Peers, C., Effects of doxapram on ionic currents recorded in isolated type I cells of the neonatal rat carotid body. Brain Res, 1991. 568(1-2): p. 116-22.

[3]. Anderson-Beck, R., et al., Doxapram stimulates dopamine release from the intact rat carotid body in vitro. Neurosci Lett, 1995. 187(1): p. 25-8.

Nigericin sodium salt | Senicapoc | E-4031 | 4-AMINOPYRIDINE | Ginsenoside Rg3 | TRAM-34 | Dofetilide | PAP-1 | Minoxidil | Flufenamic Acid | Flupirtine maleate | NS-1619 | Endoxifen (Z-isomer hydrochloride) | NS309 | Quinine

MOLECULAR FORMULA :

C24-H30-N2-O2

MOLECULAR WEIGHT :

378.56

WISWESSER LINE NOTATION :

T6N DOTJ A2- DT5NVTJ A2 CR& CR

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

268 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - somnolence (general depressed activity)

REFERENCE :

JPPMAB Journal of Pharmacy and Pharmacology. (Pharmaceutical Soc. of Great Britain, 1 Lambeth High St., London SEI 7JN, UK) V.1- 1949- Volume(issue)/page/year: 30,522,1978 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intravenous

DOSE :

1800 ug/kg

SEX/DURATION :

female 16 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - other effects to embryo

REFERENCE :

BJOGAS British Journal of Obstetrics and Gynaecology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.82- 1975- Volume(issue)/page/year: 84,48,1977