• 약학회지
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• 제33권3호
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• pp.141-148
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• 1989

The weak UV absorbing antihistaminics such as chlorpheniramine, triprolidine, tripelennamine and diphenhydramine were analyzed by charge-transfer spectrophotometric method. The results obtained are summarized as folows. It was possible to determine a weak UV absorbing antihistaminics using the intense charge-transfer UV bands in chloroform. Charge transfer complexes were formed in a 1:1 ratio between antihistaminics and iodine in chloroform. Linear relationship was found between absorbance and concentration in the range of $1.0\;{\times}\;10^{-5}M-5.0\;{\times}\;10^{-5}M$ for chlorpheniramine( ${\varepsilon}\;=\;2.082\;{\times}\;10^4$) and tripelennamine ( ${\varepsilon}\;=\;1.578\;{\times}\;10^4$), $1.0\;{\times}\;10^{-5}M-8.0\;{\times}\;10^{-5}M$ for triprolidine ( ${\varepsilon}\;=\;1.120\;{\times}\;10^4$) and $1.0\;{\times}\;10^{-5}M-1.0\;{\times}\;10^{-4}M$ for diphenhydramine ( ${\varepsilon}\;=\;9.900\;{\times}\;10^3$). Charge transfer complexes of chlorpheniramine, triprolidine and tripelennamine have absorption maxima at 293 nm and complex form of diphenhydramine has absorption maximum at 270 nm. By UV, IR spectra, it could be inferred that CT-complexes were formed by interaction between the basic nitrogen of antihistaminics as electron donor (non bonding electron) and iodine as electron acceptor (${\sigma}$ bonding electron).

• Journal of Pharmaceutical Investigation
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• 제1권1호
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• pp.30-33
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• 1971

Comparative studies were made on the analgesic effect of salicylamide, used individually and combined with parasympatholytics (propantheline and atropine) and antihistaminics (tripelennamine, diphenhydramine) as regards the analgesic effect (in thermal contact method) were examined by its oral administration with each combined drug to mouse (three assumption cross-over test), and the following effects were found. 1. The increasing order of the parasympatholytics to the analgesic effect of salicylamide is as follows: propantheline>atropine. 2. The increasing order of the antihistaminics to the analgesic effect of salicylamide is as follows: chlorpheniramine>diphenhdramine>tri pelennamine. In the ratio '1 : 1' salicylamide to parasympatholytics and antihistaminics, the analgesic effect of salicylamide was more increase than the other ratio in this study.

• Archives of Pharmacal Research
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• 제13권3호
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• pp.215-220
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• 1990

Two different, derivative spectrophotometric and gas-liquid chromatographic, procedures for direct quantitation of caffeine and some commonly dispensed antihistaminics in bulk forms, in their laboratory prepared mmixtures and in dosage formulations, have been investigated. The limit, sensitivity reproducibility and accuracy of each method were studied for each individual drug substance and in some usual pharmaceutical formulations.

• 약학회지
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• 제32권2호
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• pp.101-111
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• 1988

$[^3H]$ Quinuclidinyl benzilate(QNB) binding assays were performed in the dog ventricular sarcolemma fraction enriched approx. 32-fold in sarcolemma compared to the starting homogenate to elucidate the effect of antihistaminics on cardiac muscarinic receptor. Chlorpheniramine(CHP) inhibited specific binding of $[^3H]$QNB and delayed the equilibrium binding. The rate constants at $37^{\circ}C$ for formation and dissociation of the QNB receptor complex were $0.38{\times}10^9\;M^{-1}$ and $1.6{\times}10^{-2}\;min^{-1}$, respectively. The mean value for the dissociation constant from the pairs of the rate constants was 43. 2 pM and this value was similar to the value(44.8pM) determined from Scatchard analysis. CHP decreased association rate constant, indicating increase in $K_D$ value. Decrease in affinity without affecting the binding site concentration$(B_{max})$ for $[^3H]$QNB binding by CHP was also demonstrated by Scatchard analysis. $K_i$ values for $H_i$-blockers that inhibited specific $[^3H]$QNB binding were $0.02{\sim}4.8{\mu}M$. Cimetidine with $K_i$ value of $230{\mu}M$, however, was ineffective in displacing $[^3H]$QNB binding at concentration of $50{\mu}M$. The Hill coefficient for $H_1$-blockers were about one. The results indicate that $H_1$-antihistaminics inhibit $[^3H]$ QNB binding by interaction with myocardiac muscarinic cholinergic receptor and anticholinergic side effects of these drugs are mainly due to this receptor blocking mechanism.

• Archives of Pharmacal Research
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• 제14권2호
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• pp.181-187
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• 1991

The muscarinic antagonist 1-[benzilic 4, 4'-$[^3H]$ QUINUCLIDINYL BENZILATE $([^3H]$ QNB) bound to a single class of muscarinic receptors with high affinity in rabbit ileal membranes. The $K_D\;and\;B_{ max}$ values for $([^3H]$ QNB calculated from analysis of saturation isotherms were 52.5 pM AND 154 fmol/mg, respectively. Chlopheniramine (CHP), histamine $H_1$ blocker, increased $K_D$ vlue for $([^3H]$QNB without affecting the binding site concentrations and Hill coefficient. The $K_i$ value of CHP for inhibition of $([^3H]$QNB binding in ileal membranes was 1.44\mu{M}$ and the pseudo-Hill coefficient for CHP was close to unit. In the functional assay carbachol, muscarinic agonist, increased the contractile force of ileum with $ED_{50}$ value of $0.11\mu{M}$. CHP caused the rightward shift of the dose-response curve to carbachol. The $pA_2$ value of CHP determined from Schild analysis of carbacholinduced contraction was 5.77 and the slope was unity indicating competitive antagonism with carbachol. The dissociation constant $(K_i)$ of CHP obtained in competitive experiments with $([^3H]$ QNB was similar to the $K_A$ value (1.69 \mu{M)}$ of CHP as inhibitor of carbachol induced contraction in rabbit ileum. This result suggest that the binding of $H_i$ blocker. CHP, vs $([^3H]$QNB to muscarinic receptors in ileal membranes represents an interaction with a receptor of physiological relevance.

• 약학회지
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• 제37권4호
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• pp.397-407
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• 1993

The muscarinic antagonist l-[benzilic-4,4'-$^3H$]quinuclidinyl benzilate([$^3H$]QNB) bound to a single class of muscarinic receptor with high affinity in guinea pig ileal membranes. The $K_{D}$ and B$_{max}$ values for [$^3H$]QNB calculated from analysis of saturation isotherms were 54 pM and 156fmol/mg, respectively. H$_{1}$-blockers inhibited [$^3H$]QNB binding to ileal membranes with $K_{i}$ values ranged from 0.008 $\mu{M}$ to 1.6 $\mu{M}$. The pseudo-Hill coefficients of H$_{1}$-blockers for inhibition of [$^3H$]QNB binding to the ileal membranes were close to unit. The $K_{i}$ values for H$_{1}$-blockers were similar to the $K_{M}$ values calculated by Schild plot of functional data obtained from inhibition of the carbachol-induced contraction in guinea-pig ileum, suggesting that binding of H$_{1}$-blockers vs [$^3H$]QNB in ileal membranes represents an interaction with a receptor of physiological relevance. The $K_{H}$ values of H$_{1}$-blockers for H$_{1}$-receptor estimated from inhibition of the histamine-induced contraction were the range of 0.15 nM to 56.5 nM. The $K_{M}$/K$_{H}$ ratio of H$_{1}$-blockers varied over a wide range of 3 to 2300. Thus, the antihistaminic potencies of H$_{1}$-blockers do not correlate with their antimuscarinic potencies, which suggest that antihistamines have different antimuscarinic potencies in therapeutic blood levels causing similar antiallergic effect. Among 13 traditional antihistaminics examined in this study, drug having the highest and the lowest $K_{M}$/K$_{H}$ ratio is triprolidine and diphenidol, respectively. The present results demonstrate that the antimuscarinic property of antihistamines is not necessary for their antiallergic effect, and data on the affinity of antihistamines for muscarinic and H$_{1}$-receptors can be an important parameter in the selection and evaluation of these drugs.

• Journal of Pharmaceutical Investigation
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• 제1권1호
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• pp.78-84
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• 1971

The comparative studies were made on Salicylamide, used individually and compounded with antihistaminics as regards. (1) the absorption rate through isolated rat small intestine (in vitro) (2) the absorption rate through rat small intestine (in vivo), and the following effects were found. 1. The Absorption velosity of 2 m Mole gm. of salicylamide in the small intestine were decreased, when the agents compounded with tripelennamine indicating the greatest absorption inhibition in the case of m Mole gm. of tripelennamine. 2. The Absorption velosity of 2m Mole gm. of salicylamide in the small intestine were decreased, when the agents compounded with diphenhydramine indicating the greatest absorption inhibition in the case of 2m Mole gm. of diphenhydramine. 3. The Absorption velosity of 2m Mole gm. of salicylamide in the small intestine were increased, when the agents compounded with chlorpheniramine indicating the greatest absorption augmentation in the case of 0.2m Mole gm. of chlorpheniramine.

• 대한한방내과학회지
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• 제21권1호
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• pp.181-184
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• 2000

Dizziness is one of common diseases clinically, it is defined as a hallucination or an illusion of motion that causes sensation disorder of circumstance, and described as circulatory. rotatory leaning. shaking sensation. In particular, benign paroximal positional vertigo(BPPV) is one of peripheral vertigo, it causes dizziness due to debris which has collected within a part of the inner ear. Chemically, debris are small crystals of calcium carbonate. They are derived from structures in the ear called 'otoliths' that have been damaged by head injury, infection, or other disorder of the inner ear, or degenerated because of advanced age. The symptoms of BPPV include dizziness or vertigo, lightheadedness, imbalance, and nausea, Activities which bring on symptoms will vary in each person, but symptom are almost always precipitated by a position change of the head or body. As for treatment of vertigo, it is differentiated as excess in the upper and deficiency in the lower(上實下虛) and treated in oriental medicine and are used to stability. antihistaminics . anticolinergics . vestibule control drug of GABA system in western medicine. Moreover, Dix-hallpike maneuver is applicated in diagnosis and treatment of BPPV patients. A case of dizziness patient suggested benign paroximal positional vertigo who is diagnosed as weakly dizziness(虛暈)showed prominent improvement by Jaeumkunbitang-gamibang(滋陰建脾湯) and Dix-hallpike maneuver.

• 대한핵의학회지
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• 제1권2호
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• pp.41-59
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• 1967

This study was aimed; firstly to observe various clinical symptomatology with reiation to the number of Ancylostoma duodenale larvae orally given to the human beings, secondly to evaluate the effects of some drugs like steroid hormones, antihistaminic3 and antitussives, and, thirdly to study the influences of some iron compounds in prevention and treatment of anemia of such origin. Ten healthy volunteers free from the previous history of hookworm infection were divided into 4 groups, to whom various numbers of actively moving filariform Ancylostoma duodenale larvae were orally given; 500 to 4 cases, 250 to 3 cases and 100 to 3 cases. Following were the results: 1. Clinical symptomatology 1. The most frequently encountered symptoms and signs were general malaise, cough and hoar seness. The tracheal itching and pain low back pain, arthralgia, sputum and salivation, acid belching, loss of appetite, abdominal pain and vomiting were also noted. 2. If the larger number of the larvae was given, the clinical symtomatology was more severe. 3. Prednisolone medication caused some improvement of such symptomatology, while the antihistaminics and antitussives like codeine or ephedrine were ineffective. 4. In volunteers whose nutritional conditions were rather poor appeared to show more severe symptomatology. 2. Effects of iron compounds 1. The oral administration of ferrous fumarate induced a slight increase of serum iron levels in the initial stage of the infection, then a decrease from $15{\sim}20$ days later and a recovery after 2 months. 2. The intravenous administration of saccharated ferric oxide induced a steady upkeep of the serum iron levels. 3. The hemoglobin contents also showed the upkeeps after either the oral or intravenous administration of the iron compounds. 4. The iron compounds, therefore, are considered to have the preventive as well as the therapeutic effects on hookworm anemia, which may strongly suggest that hookworm anemia is essentially the iron deficiency type. 3. Hematological changes 1. The severity of hookworm anemia generally correlated with the number of larvae given. 2. The moderate leucocytosis was observed in all cases regardless of the number of larvae given, which reached to a peak in $25{\sim}35$ days. 3. Eosinophilia was observed in all cases, but was more severe in cases given larger number of larvae, which was slightly less evident after the medication of prednisolone. 4. Red cell survival time The red cell survival time determined by $^{51}Cr$ was generally in the normal ranges except for the severe anemia patients.

• 약학회지
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• 제34권4호
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• pp.224-237
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• 1990

A single uniform population of specific, saturable, high affinity binding site of $[^3H]QNB$ guinuclidinyl benzilate(QNB) was identified in the rat cerebral microsomes. The Kd value(37.2 pM) for $[^3H]QNB$ calculated from the kinetically derived rate constants was in agreement with the Kd value(48.9 pM) determined by analysis of saturation isotherms at various receptor concentrations. Dimenhydrinate(DMH), histamine $H_1-blocker$, increased Kd value for $[^3H]QNB$ QNB without affecting the binding site concentrations and this effect resulted from the ability of DMH to slow $[^3H]QNB-receptor$ association. Pirenzepine inhibition curve of $[^3H]QNB$ binding was shallow(nH = 0.52) indicating the presence of two receptor subtypes with high ($M_1-site$) and low($M_2-site$) affinity for pirenzepine. Analysis of these inhibition curves yielded that 68% of the total receptor populations were of the $M_1-subtype$ and the remaining 32% of the $M_2-subtype$. Ki values for the $M_1-$ and $M_2-subtypes$ were 2.42 nM and 629.3 nM, respectively. Ki values for $H_1-blockers$ that inhibited $[^3H]QNB$ binding varied with a wide range ($0.02-2.5\;{\mu}M$). The Pseudo-Hill coefficients for inhibition of $[^3H]QNB$ binding by most of $H_1-blockers$ examined except for oxomemazine inhibition of $[^3H]QNB$ binding were close to one. The inhibition curve for oxomemazine in competition with $[^3H]QNB$ was shallow(nH = 0.74) indicating the presence of two receptor populations with different affinities for this drug. The proportion of high and low affinity was 33:67. The Ki values for oxomemazine were $0.045{\pm}0.016\;{\mu}M$ for high affinity and $1.145{\pm}0.232\;{\mu}M$ for low affinity sites. These data indicate that muscarinic receptor blocking potency of $H_1-blockers$ varies widely between different drugs and that most of $H_1-blockers$ examined are nonselective antagonist for the muscarinic receptor subtypes, whereas oxomemazine might be capable of distinguishing between subclasses of muscarinic receptor.