PHARMACOLOGICAL STUDIES OF IMIDAZOLINE DERIVATIVES. I. A COMPARISON OF THE EFFECT ON PRE- AND POSTSYNAPTIC α-ADRENOCEPTORS IN THE RAT VAS DEFERENS
スポンサーリンク
概要
- 論文の詳細を見る
The effects of 8 imidazoline derivatives on pre- and postsynaptic α-adrenoceptors and [^3H] norepinephrine release were investigated in the rat vas deferens and were compared with those of reference drugs, yohimbine, phentolamine, tolazoline, and prazosin. K-6341 and K-6343 activated postsynaptic α_1-adrenoceptor and were antagonized by prazosin. The order of potency series as α_1-antagonist, prazosin > phentolamine > yohimbine > K-4011 > K-3827 > K-4300,tolazoline was found in antagonism against phenylephrine. Many derivatives exhibited an antagonistic action against clonidine, and the potency series as α_2-antagonist was revealed as follows : phentolamine > yohimbine > K-3827 > K-4011 > K-6341 > K-6343 > K-4300,tolazoline > prazosin > K-4299. The antagonistic effect was more selective on presynaptic (α_2) than postsynaptic (α_1) adrenoceptor and the rank order of selectivity (K_B-post/K_B-pre) was K-3827 > yohimbine > K-4011 > tolazoline, K-4300 > phentolamine > prazosin. Imidazoline derivative increased [^3H]norepinephrine release, the actions of K-3827,K-6341 and K-4300 being particularly potent. From these results, the structure-activity relationship was summarized. First, when 2', 3'-methylenedioxyphenyl group is connected with the imidazoline ring via an amino or methylene residue, these compounds become α_1-agonist. Secondly, when the methylenedioxyphenyl group and the imidazoline ring are connected via an amino residue, these compounds show a weak agonistic and potent antagonistic characteristics at the presynaptic α_2-adrenoceptor. Thirdly, an addition of a methylenedioxy radical to the phenyl ring increased the affinity of the compounds to presynaptic α_2-receptor.
- 公益社団法人日本薬学会の論文
著者
-
Goto Katsutoshi
Departments of Internal Medicine, Surgery, Pharmacology, University of Tsukuba
-
KASUYA YUTAKA
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo
-
Goto Katsutoshi
Department Of Pharmacology Institute Of Basic Medical Sciences The University Of Tsukuba
-
Kasuya Y
Department Of Pharmacology Hoshi University School Of Pharmaceutical Sciences
-
AKATSUKA KENICHI
Department of Pharmacology, Meiji College of Pharmacy
-
Akatsuka Kenichi
Department Of Pharmacology Meiji College Of Pharmacy
-
Kasuya Yutaka
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
-
Goto Katsutoshi
Department Of Ophthalmology Kawasaki Medical School
関連論文
- -0902- ENDOTHELIN RECEPTOR SUBTYPES IN THE PULMONARY ARTERIAL SMOOTH MUSCLES AND BRONCHIAL SMOOTH MUSCLES IN HUMANS(PROCEEDINGS OF THE 59th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY)
- 0882 ENDOTEHLIN RECEPTOR SUBTYPES IN HUMAN UTERINE SMOOTH MUSCLES
- PJ-393 Changes of Myocardial Endothelin-1 Level during the Formation of Exercise Training-induced Cardiac Adaptation(Exercise test/Cardiac rehabilitation-3 (IHD) PJ66,Poster Session (Japanese),The 70th Anniversary Annual Scientific Meeting of the Japanese
- PE-243 Endothelin Receptor Antagonist Ameliorates the Cardiac Dysfunction, Decreased Cardiac VEGF Signaling and Inadequate Coronary Collateral Development in Early Diabetic Rats(Diabetes/Obesity/Metabolic syndrome-8 (H) PE41,Poster Session (English),The 7
- PE-188 Dual Endothelin Receptor Antagonist Reverses the Upregulated VEGF-KDR Axis in Frontal Cortex of SHR-SP without Modulating the Cerebral Blood Flow(Cerebrovascular circulation/Stroke-2 (IHD) PE32,Poster Session (English),The 70th Anniversary Annual S
- OE-298 Eicosapentaenoic Acid, a Major Component of Fish Oil, Prevents the Progression of Endothelin-1-Induced Cardiomyocyte Hypertrophy through Suppressing Phosphorylated JNK(Cardiovascular pharmacology, basic/clinical-1 (H) OE50,Oral Presentation (Englis
- -0827-PLASMA CONCENTRATIONS OF ENDOTHELIN-1 AMD BIG ENDOTHELIN-1 IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION : THE 54th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY
- Poor Survival of Cardiomyopathic Hamsters with CHF Is Greatly Improved by Combined Treatment with Endothelin (ET)-A Receptor Antagonist and ACE Inhibitor
- IS097 Chronic treatment with endothelin inhibitor greatly improves survival in hamsters with heart failure due to dilated cardiomyopathy : increased expression of endothelin-1 in failing heart
- ATTENUATION OF THE DEVELOPMENT OF HYPERTENSION IN SPONTANEOUSLY HYPERTENSIVE RATS BY CHRONIC ORAL ADMINISTRATION OF EICOSAPENTAENOIC ACID
- OE-176 Endothelin-1 Induces the Expressions of VEGF and Its Receptors (Flt-1 and Flk-1) in Neonatal Cardiomyocytes in Vitro Dosedependently(Neurohumoral factors-1 (H) OE30,Oral Presentation (English),The 70th Anniversary Annual Scientific Meeting of the J
- PJ-042 Effects of Athletic Strength- and Endurance-exercise Training on Aortic Stiffness and Plasma Endothelin-1 Concentration in Young Humans(Exercise test/Cardiac rehabilitation-5 (IHD) PJ7,Poster Session (Japanese),The 70th Anniversary Annual Scientifi
- P784 DOES MYOCARDIAL ENDOTHELIN-1 PARTICIPATE IN THE MODULATION OF CARDIAC FUNCTION DURING EXERCISE?
- P627 EXPRESSION OF ENDOTHELIN RECEPTOR SUBTYPBS AND ANGIOTENSIN RECEPTOR SUBTYPES IN THE HEART OF RATS WITH CHRONIC HEART FAILURE
- -1090-IMPORTANCE OF CALCITONIN GENE-RELATED PEPTIDE (CGRP)-CONTAINING NERVES IN THE REGULATION OF HUMAN VASCULAR TONUS : THE 54th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY
- Cardiac hypertrophic respones by acute prenaure-overload in reduced in cardiomyocyte-upecitic endothelin-1-knockout mice
- Cardiovascular Effects of Endothelin : ROLES OF VASCULAR ENDOTHELIUM IN REGULATION OF CARDIOVASCULAR SYSTEM
- Elucidation With the Protease α-Chymotrypsin of the Inhibitory Modulating Action of Endogenous Neuropeptide Y Over Sympathetic Neurotransmission in Rat Vas Deferens
- A Comparative Study of Changes in Innervation and Development of Supersensitivity in the Rat Vas Deferens after Various Procedures
- INHIBITORY EFFECTS OF HISTAMINE ON CONTRACTION INDUCED BY TRANSMURAL STIMULATION IN RAT VAS DEFERENS
- PATHOPHYSIOLOGICAL ROLES OF ENDOTHELIN-1 IN PULMONARY HYPERTENSIVE RATS
- Decreases in Exercise Capacity, Myocardial Energy Metabolism, and Survival in Rats with CHF Are Greatly Improved by Endothelin-A Receptor Antagonist
- Endogenous endothelin (ET)-1 depresses both NOS activity and NO production in the kidney during exercise
- 0894 EXPRESSION OF ENDOTHELIN RECEPTOR MESSENGER RNA IN THE CONGESTIVE LUNG IN RATS WITH CHRONIC HEART FAILURE
- 0884 ENDOTHELIN CONVERTING ENZYME AND ANGIOTENSIN CONVERTING ENZYME IN THE HEART OF RATS WITH CHRONIC HEART FAILURE
- 0804 EXPRESSION OF ENDOTHELIN-1 mRNA IN THE HEART OF PATHOLOGICAL HYPERTROPHY OR PHYSIOLOGICAL HYPERTROPHY
- 0234 Treatment with an Endothelin Receptor Antagonist Ameliorates Chronic Heart Failure in Rats and Inhibits the Alteration of the Expression of Cardiac Genes
- STUDIES ON NITROSAMINE FORMATION BY THE INTERACTION BETWEEN DRUGS AND NITRITE. I. : Measurement of the amount of nitrosamine formed in rat and guinea pig stomachs.
- Involvement of α_2-Adrenergic Receptors in the Vagal Reflex-Induced Tracheal Constriction
- INHIBITION OF THE VAGAL REFLEX-INDUCED TRACHEAL CONSTRICTION BY PSYCHOTROPIC DRUGS
- Mechanisms of Increased Responses of the Aorta to α-Adrenoceptor Agonists in Streptozotocin-Induced Diabetic Rats
- PHARMACOLOGICAL STUDIES OF IMIDAZOLINE DERIVATIVES. III. ACTIONS ON CARDIOVASCULAR SYSTEM AND ACUTE TOXICITY
- PHARMACOLOGICAL STUDIES OF IMIDAZOLINE DERIVATIVES. II. AGONISTIC AND ANTAGONISTIC ACTIONS ON α-ADRENOCEPTORS IN VARIOUS SMOOTH MUSCLE PREPARATIONS
- PHARMACOLOGICAL STUDIES OF IMIDAZOLINE DERIVATIVES. I. A COMPARISON OF THE EFFECT ON PRE- AND POSTSYNAPTIC α-ADRENOCEPTORS IN THE RAT VAS DEFERENS
- THE DEVELOPMENT OF A NONLINEAR MODEL TO DESCRIBE THE BLOOD GLUCOSE RESPONSE FOR THE DETERMINATION OF PRANDIAL INSULIN INFUSION
- EVALUATION OF THE BOLIE MODEL DESCRIBING BLOOD GLUCOSE RESPONSE FOR THE APPLICATION TO CONTINUOUS SUBCUTANEOUS INSULIN INFUSION
- THE DEVELOPMENT OF NONLINEAR MODEL TO DESCRIBE THE BLOOD GLUCOSE RESPONSE FOR THE DETERMINATION OF PRANDIAL INSULIN INFUSION
- PHARMACOKINETICS AND PHARMACODYNAMICS OF SUBCUTANEOUS INSULIN INJECTION IN DEPANCREATIZED DOGS
- Further Studies Concerning Possible Transmitters from NANC Nerves in the Circular Muscle of the Rat Stomach Fundus
- PLATELET ACTIVATING FACTOR : LACK OF DIRECT CARDIAC ACTION AND POSSIBLE TRANSMITTER RELEASE FROM CARDIAC SYMPATHETIC NERVE ENDINGS AT HIGH CONCENTRATIONS. ELECTROPHYSIOLOGICAL AND MECHANICAL STUDIES WITH GUINEA PIG VENTRICULAR MYOCARDIUM
- Effects of Calmodulin Antagonist (W-7) on Phorbol Ester (PMA)-induced Contractile Response in Isolated Rat Aorta
- Effect of phorbol 12, 13-dibutyrate on smooth muscle tone in rat stomach fundus
- Diabetes-related changes in contractile responses of stomach fundus to endothelin-1 in streptozotocin-induced diabetic rats
- MUTAGENICITY TEST OF ANTITHYROID AGENT (VI) THE EFFECT OF METHIMAZOLE IN THE GERM CELLS OF THE MOUSE
- Endothelin ET_A and ET_B Receptors Mediate Endothelin-1-Induced Apamin-Sensitive Relaxation in the Guinea Pig Ileum
- POTENTIATION BY BOVINE SERUM ALBUMIN (BSA) OF ENDOTHELIUM-DEPENDENT VASODILATOR RESPONSE TO ACETYL GLYCERYL ETHER PHOSPHORYLCHOLINE (AGEPC)
- Prominent induction of cyclin B1 in G2/M renal cancer cells with butyrolactone 1
- Differences in cell kinetic changes among renal cancer cell lines treated with interferon-α
- The effect of papaverine on morphologic differentiation,proliferation and invasive potential of human prostatic cancer LNCaP cells
- -0705- Endothelin-1 and cardiac hypertrophy due to pressure or volume overload in rats(PROCEEDINGS OF THE 59th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY)
- -0657- Effects of an endothelin-A receptor antagonist on the pulmonary hypertension caused by congestive heart failure in Rats(PROCEEDINGS OF THE 59th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY)
- The Production of Endothelin-1 in the Heart is Altered in Rats with Heart Failure
- The Production of Endothelin-1 in the Hypertrophied Rat Heart due to Pressure or Volume Overload
- RENAL MICROSOMAL N-NITROSODIMETHYLAMINE DEMETHYLASE DETERMINED BY A SENSITIVE RADIOMETRIC METHOD
- STUDIES ON NITROSAMINE FORMATION BY THE INTERACTION BETWEEN DRUGS AND NITRITE. II. : Hepatotoxicity by the simultaneous administration of several drugs and nitrite.
- Orexin Receptor Type-1 Couples Exclusively to Pertussis Toxin-Insensitive G-Proteins, while Orexin Receptor Type-2 Couples to Both Pertussis Toxin-Sensitive and *Insensitive G-Proteins
- EFFECTS OF HYPOXIA AND REOXYGENATION ON TISSUE ATP LEVEL AND ELECTRICAL AND MECHANICAL FUNCTION OF ISOLATED GUINEA PIG VENTRICULAR MUSCLES.
- EFFECTS OF HYPOXIA AND METABOLIC INHIBITORS ON THE ELECTRICAL AND MECHANICAL ACTIVITIES OF ISOLATED GUINEA PIG PAPILLARY MUSCLES
- ELECTROPHYSIOLOGICAL EFFECTS OF A NEW ANTIARRHYTHMIC AGENT, LORCAINIDE, ON THE ISOLATED CARDIAC MUSCLE FIBER AS COMPARED WITH DISOPYRAMIDE
- Effects of L-Tryptophan on the Effects of Antitussives
- Effects of Double-enkephalin (Biphalin), an Enkephalin Analogue, on Respiration and the Cough Reflex in Rats
- Effect of Diabetes on the Morphine-Induced Inhibition of Gastrointestinal Tranist
- Bosentan, a novel synthetic mixed-type endothelin receptor antagonist, attenuates acute gastric mucosal lesions induced by indomethacin and HCl in the rat: Role of endogenous endothelin-1
- L-arginine and endogenous nitric oxide protect the gastric mucosa from endothelin-1-induced gastric ulcers in rats
- NEGATIVE CHRONOTROPIC EFFECT OF DIBUTYRYL CYCLIC AMP ON THE CULTURED CHICK EMBRYONIC HEART CELLS AND THE PROLONGATION OF THE ACTION POTENTIAL DURATION
- THE MECHANISM OF AGGRAVATION OF INDOMETHACIN-INDUCED GASTRIC ULCERS BY ADRENALECTOMY IN THE RAT
- Propranolol Blocks Cocaine-Induced Potentiation of the Contraction in the Smooth Muscle of the Rat Vas Deferens
- EFFECTS OF SMOOTH MUSCLE STIMULANTS ON I-ISOPRENALINE-β-ADRENOCEPTOR INTERACTION IN TAENIA FROM GUINEA PIG CAECUM
- Combination of endothelin-A (ET_A) receptor inhibitor and prostacyclin (PGI_2) analogue is preferable to each drug alone for pulmonary hypertension (PH)
- Corresponding distributions of increased endothelin-B receptor expression and increased endothelin-1 expression in the aorta of apolipoprotein E-deficient mice with advanced atherosclerosis
- EFFECTS OF VARIOUS DRUGS AND VAGOTOMY ON INDOMETHACIN-INDUCED GASTRIC ULCERS IN THE RAT
- INHIBITORY ALPHA-ADRENERGIC ACTION OF PHENYLEPHRINE IN GUINEA PIG TAENIA CAECUM
- EFFECTS OF COCAINE ON Ca-MOBILITY IN MICROSOMAL FRACTION FROM RAT VAS DEFERENS
- EFFECTS OF ACETYLCHOLINE AND HISTAMINE ON MECHANICAL ACTIVITY OF RABBIT TAENIA COLI, Ca-INCORPORATION AND Ca-RELEASE IN ITS MICROSOMAL FRACTION
- NONSPECIFIC RELAXATION OF INTESTINAL SMOOTH MUSCLE INDUCED BY ANTISPASMODICS AND MOVEMENT OF CALCIUM IONS
- EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS ON GLYCOGEN PHOSPHORYLASE ACTIVITY IN DEPOLARIZED TAENIA CAECUM OF GUINEA PIG
- EFFECTS OF NONSPECIFIC SMOOTH MUSCLE RELAXANTS ON TISSUE CONCENTRATIONS OF HIGH ENERGY PHOSPHATES AND MECHANICAL ACTIVITY OF NORMAL POLARIZED AND DEPOLARIZED INTESTINAL SMOOTH MUSCLES FROM GUINEA PIG
- POSSIBLE ROLE OF ENDOTHELIUM IN THE VASODILATOR RESPONSE OF RAT THORACIC AORTA TO PLATELET ACTIVATING FACTOR (PAF)
- STUDIES ON THE HYPOTENSIVE EFFECTS OF PLATELET ACTIVATING FACTOR (PAF, 1-o-ALKYL-2-ACETYL-sn-GLYCERYL-3-PHOSPHORYLCHOLINE) IN RATS, GUINEA PIGS, RABBITS, AND DOGS
- ELECTROPHYSIOLOGICAL AND MECHANICAL STUDIES ON THE CARDIAC EFFECTS OF A HISTAMINE H_2 RECEPTOR ANTAGONIST, CIMETIDINE, IN THE ISOLATED GUINEA PIG MYOCARDIUM
- EVIDENCE FOR A DIRECT ACTION OF X-537A ON THE CARDIAC PLASMA MEMBRANE AS AN IONOPHORE
- Preservation of Endothelium-Dependent Vascular Relaxation in Cholesterol-Fed Mice by the Chronic Administration of Prazosin or Pravastatin
- INHIBITION BY PROPRANOLOL OF HIGH POTASSIUM-INDUCED CONTRACTIONS IN THE RAT VAS DEFERENS
- Basic and Therapeutic Relevance of Endothelin-Mediated Regulation
- Molecular Pharmacology and Pathophysiological Significance of Endothelin
- DEPLETION OF CALCITONIN GENE-RELATED PEPTIDE (CGRP) BY CAPSAICIN IN CEREBRAL ARTERIES
- A COMPARATIVE STUDY OF CHANGES IN INNERVATION AND DEVELOPMENT OF SUPERSENSITIVITY IN THE RAT VAS DEFERENS AFTER VARIOUS PROCEDURES
- EFFECTS OF VARIOUS DRUGS AND EXTRINSIC DENERVATION ON THE NON-ADRENERGIC INHIBITORY NEURONS IN THE RAT STOMACH
- RENAL TOXICITY OF ADENOSINE 3', 5'-CYCLIC MONOPHOSHATE IN MICE.
- ACUTE TOXICITY OF ADENOSINE 3', 5'-CYCLIC MONOPHOSPHATE
- CARDIOTONIC EFFECT OF PHTHALAZINOL (EG-626) IN THE ISOLATED GUINEA PIG MYOCARDIUM : MECHANICAL AND ELECTROPHYSIOLOGICAL STUDY
- 1123 Treatment with an Endothelin Receptor Antagonist Ameliorates Chronic Heart Failure in Rats
- -P402- Study of endothelin-1-like immunoreactivity in the lung of rats with pulmonary hypertension caused by monocrotaline(PROCEEDINGS OF THE 59th ANNUAL SCIENTIFIC MEETING OF THE JAPANESE CIRCULATION SOCIETY)
- PULMONARY VASCULAR RESPONSES TO VARIOUS VASODILATOR AGENTS IN RATS WITH PULMONARY HYPERTENTSION
- CARDOVASCULAR EFFECTS OF AMYLIN,A NOVEL PANCREATIC HORMONE
- EFFECTS OF 15(S)-15-METHYL-PGE2 METHYL ESTER ON HEALING OF CHRONIC GASTRIC AND DUODENAL ULCERS IN RATS
- DESENSITIZATION OF GUINEA PIG TRACHEAL MUSCLE PREPARATION TO BETA-ADRENERGIC STIMULANTS BY A PRECEDING EXPOSURE TO A HIGH DOSE OF CATECHOLAMINES
- INFLUENCE OF SURGICAL SYMPATHECTOMY ON GASTRIC SECRETION AND ULCERATION IN RATS
- FURTHER STUDIES ON BIOCHEMICAL ACTIVE SUBSTANCES IN URINE, INCREASING WITH FATIGUE DUE TO PHYSICAL EXERCISE
- Analysis of New Imidazoline Derivative-Induced Increase in the Maximum Response to Norepinephrine in the Rat Vas Deferens