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Journal of Pharmacology And Experimental Therapeutics, Vol. 189, Issue 1, 1-11, 1974
Copyright © 1974 by American Society for Pharmacology and Experimental Therapeutics

SELECTIVE RESPIRATORY STIMULATING ACTION OF DOXAPRAM COMPARED TO PENTYLENETETRAZOL

Kenneth Hirsh 1 and S. C. Wang 2

1 Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York
2 Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York

The effects of doxapram and pentylenetetrazol on medullary respiratory and nonrespiratory neurons were studied in midcollicular decerebrate cats. It was found that doxapram acts on two sites: the chemoceptors and the medullary neurons. The carotid chemoceptors are most sensitive to the drug. The observed "selective" stimulation of medullary respiratory neurons evoked by small intravenous doses of 0.05 to 0.25 mg/kg was due to indirect activation of these neurons through carotid chemoceptor activation. The aortic chemoceptors play a very minor role at these doses. The direct, central neuronal stimulation is effected by large doses of doxapram. This action is nonselective. It is interesting that although doxapram does not selectively stimulate the respiratory neurons per se, a selectivity for respiratory neuron activation was demonstrated over the entire dose range studied. When the dose is increased, both medullary respiratory and nonrespiratory neurons are directly and equally stimulated, but the stimulatory effect on respiratory neurons is augmented by additional input coming from the carotid chemoceptors. Thus, the medullary respiratory neurons will always be activated more than the neighboring nonrespiratory neurons at every dose level. On the other hand, pentylenetetrazol, in the dosage range of 1.0 to 20.0 mg/kg, exhibits no selective respiratory stimulant action. It does not stimulate the carotid chemoceptors: the action is directly in the central nervous system and is nonselective.

Submitted on June 25, 1973
Accepted on December 17, 1973




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[Abstract] [Full Text] [PDF]


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Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics.