[Effects of 1-ethyl-4-(2-morpholinoethyl)-3, 3-diphenyl-2-pyrrolidinone hydrochloride hydrate (doxapram) on the transmural stimulation and reactiontonicotine of the isolated guinea pig heart atrium].
It has been reported that doxapram exhibits a remarkable stimulating effect on respiration in humans and various experimental animals. The present experiment was an attempt to investigate whether or not doxapram inhibits an atrial arrest induced by transmural stimulation and exogenously applied nicotine. Doxapram and dimorpholamine used as comparative agents showed transient and slightly positive responses followed by a negative one in the atrium preparation. Transmural stimulation under a condition of 30 V intensity with 0.3 msec duration at a frequency of 10 Hz for 2 sec caused an atrial arrest for about 3 sec followed by negative chronotropic and inotropic responses, and a positive one. All responses caused by transmural stimulation were hardly affected by pretreatment with doxapram at a concentration of 10(-5) g/ml or less, while dimorpholamine at a high concentration (10(-5)g/ml) showed an inhibition of atrial arrest and following negative responses. Negative chronotropic and inotropic responses caused by an application of nicotine were significantly inhibited by pretreatment with doxapram or dimorpholamine. Both doxapram and dimorpholamine at higher concentrations also inhibited the positive responses of the atrium caused by nicotine. Neither doxapram nor dimorpholamine affected the ACh-induced responses. NA-induced responses were uneffected by pretreatment with doxapram, while the responses were slightly potentiated by dimorpholamine. The action mechanisms of doxapram and dimorpholamine are discussed.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004315:Doxapram / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology
D009538:Nicotine; D004315:Doxapram; D000109:Acetylcholine; D009638:Norepinephrine