Medical Journal of the Islamic Republic Of Iran
مجله پزشکی جمهوری اسلامی ایران
Med J Islam Repub Iran
Medical Sciences
http://mjiri.iums.ac.ir
2
journal2
1016-1430
2251-6840
8
10.18869/mjiri
14
8888
13
en
jalali
1376
5
1
gregorian
1997
8
1
11
2
online
1
fulltext
en
ENHANCED HISTAMINE H I RECEPTOR BLOCKADE WITH CHLORPHENIRAMINE IN THE ASTHMATIC TRACHEO-BRONCHIAL TREE: FURTHER EVIDENCE FOR INCREASED DRUG DELIVERY IN ASTHMA
Physiology
Physiology
Original Research: Basic Science in Medicine
Original Research: Basic Science in Medicine
We have measured the competitive antagonistic effect of chlorpheniramine
in bronchi of 8 normal and 12 asthmatic subjects. Classical pharmacological
theory states that the degree of competitive antagonism depends only upon 1)
antagonist concentration at the receptor, and 2) receptor affinity. Delivery and
affinity also influence agonist responsiveness, but measurement of bronchial
antagonism allows study of these factors in isolation. Bronchial responsiveness to
histamine was measured as the dose required to produce a 35% fall in specific
conductance (sGaw), called PD35• On different days, 2 measurements of control
PD35 were made on each subject. Measurements of PD35 were also repeated after
inhalation of 1.45 mg chlorpheniramine and intravenous injection of 0.17 mg/kg
chlorpheniramine. Antagonist effect of chlorpheniramine was measured as Dose
Ratio-l (DR-I), where DR= PD35 after chlorpheniramine/control PD35• Geometric
mean of DR -1 with inhaled chlorpheniramine in asthmatic subjects (5.8) was 6.8
times that of normal subjects (0.86) (p= 0.002), and DR-l with intravenous
chlorpheniramine in asthmatic subjects (4.4) was 2.75 times that of normal
subjects (1.6) (p=0.005). There were significant negative correlations between
PD35 and DR-I, whether chlorpheniramine was administered by inhalation (r=
-0.87, p<O.OO 1) or intravenously (r= -0.62, p<0.005). There was also a significant
correlation between DR-1 obtained by two routes of administration (r= 0.77,
p<0.001). Taken with our previous study showing enhanced antagonism with
atropine at bronchial muscarinic receptors in asthma, I these results suggest that
drug delivery by inhaled and parenteral routes may be increased in asthmatic
bronchi.
histamine HI receptors, asthma, chlorpheniramine, histamine
115
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http://mjiri.iums.ac.ir/browse.php?a_code=A-10-1-374&slc_lang=en&sid=1
MOHAMMAD H.
BOSKABADY
20031947532846006872
20031947532846006872
Yes
From the Department of Physiology, Ghaem Medical Center, Mashhad University of Medical Sciences, Mashhad, Iran
PHILLIP D.
SNASHALL
20031947532846006873
20031947532846006873
No
the Department of Medicine, Charing Cross and Westminster Medical School, Fulham Palace Road, London W68RF, UK.