-
British Journal of Pharmacology Sep 19761 The kinetics of action of some competitive muscarinic and histamine antagonists were examined on guinea-pig isolated ileum and their behaviour compared with the...
1 The kinetics of action of some competitive muscarinic and histamine antagonists were examined on guinea-pig isolated ileum and their behaviour compared with the predictions of the interaction-limited model described by Paton (1961). 2 The kinetics of antagonism were not consistent with the predictions of this model: (1) The apparent dissociation rate constant calculated from the decrease in occupancy on washout was not independent of the concentration of antagonist. (2) The dissociation rate constant of a 'slow' antagonist calculated from the change in occupancy when a 'fast' antagonist was superimposed varied with the concentration of fast antagonist. (3) If the concentration of slow antagonist was increased when the fast antagonist was superimposed so that the equilibrium occupancy of the 'slow' was the same as before, a transitional phase was observed. 3 The kinetics of antagonism were observed in longitudinal muscle strips and intact pieces of ileum, bathed in Tyrode or Krebs solution, and with isometric and isotonic recording. No evidence was found that the discrepancies between the interaction-limited model and the observed kinetics could be accounted for by the experimental method used. 4 It is therefore concluded that either access is rate-limiting in these circumstances or, if interaction is rate-limiting, some alternative interaction-limited model is required to describe the kinetics of antagonism. In either case it would seem unwise at this time to calculate antagonist-receptor rate constants from the observed kinetics of antagonism.
Topics: Animals; Antazoline; Atropine; Benzilates; Drug Interactions; Guinea Pigs; Ileum; In Vitro Techniques; Kinetics; Muscle Contraction; Pyrilamine; Quaternary Ammonium Compounds; Tropanes
PubMed: 974378
DOI: 10.1111/j.1476-5381.1976.tb07693.x -
British Journal of Pharmacology and... Mar 1960In an attempt to find agents enhancing the infiltration of isoniazid into tissues, the authors have investigated the effect of the drug on oedema due to injection of egg...
In an attempt to find agents enhancing the infiltration of isoniazid into tissues, the authors have investigated the effect of the drug on oedema due to injection of egg white into the rat paw, when it was given alone and in conjunction with histamine, antazoline, carbachol, chlorpromazine, and a pyrogen. Isoniazid increased the oedema. All the substances, except antazoline, increased the rate at which isoniazid disappeared from the blood, and they all favoured accumulation of the drug in tissues. Treatment of experimental tuberculosis with subthreshold doses of isoniazid, in conjunction with the above compounds, gave better results than when isoniazid was used alone.
Topics: Animals; Hypersensitivity; Immune System Diseases; Isoniazid; Rats; Tuberculosis
PubMed: 13841710
DOI: 10.1111/j.1476-5381.1960.tb01202.x -
Polish Journal of Pharmacology 2001The inhibitory effect of lipopolysaccharides (LPS) on contraction evoked by alpha-adrenergic stimulation is quite well-known, but molecular mechanism of this inhibition...
The inhibitory effect of lipopolysaccharides (LPS) on contraction evoked by alpha-adrenergic stimulation is quite well-known, but molecular mechanism of this inhibition is unclear. In the present study, an interaction between alpha-adrenoceptor response and LPS in rat tail artery was investigated using chemical stimulation. In the presence of LPS noradrenaline and phenylephrine, concentration-response curves were shifted to the right with a change in maximal responses. The K(A) and K(B) values calculated in the presence and absence of LPS did not differ significantly. The results strongly suggest that LPS did not change the affinity of alpha-adrenoceptors. Changes in the plot showing relationship between agonist-evoked responses and receptor occupancy in the presence of LPS and reduction of K(A)/ED50 value suggest reduction of alpha-adrenoceptor reserve. In the experiments performed on arteries without endothelium, the inhibitory effect of LPS was still present. In the presence of atropine, antazoline and indomethacin, the reduction of alpha-adrenoceptor reserve was noted, but in the presence of N-omega-nitro-L-arginine methyl ester (L-NAME), the inhibitory effect of LPS was not significant. Moreover, in LPS-pretreated arteries, in the presence of L-NAME, the increase in the receptor reserve was observed. It suggests that inhibitory effect of LPS is partially reversible. The results strongly indicate that in early endotoxemia, main inhibitory effect of LPS is connected with releasing nitric oxide and decreasing coupling between alpha1-adrenoceptor and signal induction.
Topics: Adrenergic alpha-Agonists; Adrenergic alpha-Antagonists; Animals; Arteries; Dose-Response Relationship, Drug; Endothelium, Vascular; Endotoxemia; In Vitro Techniques; Lipopolysaccharides; Male; Nitric Oxide; Norepinephrine; Phenylephrine; Prazosin; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1; Tail; Time Factors; Vasoconstriction
PubMed: 11985334
DOI: No ID Found -
British Journal of Pharmacology Sep 19921. Islets from normal mice were used to study the mechanisms by which imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in vitro. 2. Alinidine,...
1. Islets from normal mice were used to study the mechanisms by which imidazoline antagonists of alpha 2-adrenoceptors increase insulin release in vitro. 2. Alinidine, antazoline, phentolamine and tolazoline inhibited 86Rb efflux from islets perifused with a medium containing 3 mM glucose, i.e. under conditions where many adenosine 5'-triphosphate (ATP)-sensitive K+ channels are open in the beta-cell membrane. They also reduced the acceleration of 86Rb efflux caused by diazoxide, an opener of ATP-sensitive K+ channels. 3. ATP-sensitive and voltage-sensitive K+ currents were measured in single beta-cells by the whole-cell mode of the patch-clamp technique. Antazoline more markedly inhibited the ATP-sensitive than the voltage-sensitive current, an effect previously observed with phentolamine. Alinidine and tolazoline partially decreased the ATP-sensitive K+ current. 4. The four imidazolines reversed the inhibition of insulin release caused by diazoxide (through opening of ATP-sensitive K+ channels) or by clonidine (through activation of alpha 2-adrenoceptors) in a concentration-dependent manner. Only the former effect correlated with the ability of each drug to increase control insulin release stimulated by 15 mM glucose alone. 5. It is concluded that the ability of imidazoline antagonists of alpha 2-adrenoceptors to increase insulin release in vitro can be ascribed to their blockade of ATP-sensitive K+ channels in beta-cells rather than to their interaction with the adrenoceptor.
Topics: Adenosine Triphosphate; Adrenergic alpha-Antagonists; Analysis of Variance; Animals; Antazoline; Clonidine; Electrophysiology; Female; In Vitro Techniques; Insulin; Islets of Langerhans; Mice; Phentolamine; Potassium; Potassium Channels; Tolazoline
PubMed: 1358388
DOI: 10.1111/j.1476-5381.1992.tb14456.x -
Canadian Medical Association Journal Sep 1975Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled... (Clinical Trial)
Clinical Trial Comparative Study
Seven patients with chronic or recurrent supraventricular tachyarrhythmias were selected for a trial of antazoline therapy because sinus rhythm or a controlled ventricular response could not be achieved with quinidine, procainamide, digitalis or propranolol. Sinus rhythm was established by either intravenous administration of antazoline or direct-current countershock, and has been maintained in all for 4 to 16 months by oral administration of antazoline. Side effects were minor. Antazoline is a sufficiently promising antiarrhythmic agent to warrant large-scale controlled studies.
Topics: Adolescent; Adult; Aged; Antazoline; Arrhythmias, Cardiac; Chronic Disease; Clinical Trials as Topic; Digoxin; Drug Evaluation; Female; Humans; Imidazoles; Male; Middle Aged; Procainamide; Propranolol; Quinidine; Recurrence
PubMed: 1098755
DOI: No ID Found -
British Journal of Pharmacology Mar 19791 Intramural nerve stimulation elicited a powerful relaxation of the longitudinal muscle of the rabbit portal vein in the presence of atropine and guanethidine, but not... (Comparative Study)
Comparative Study
1 Intramural nerve stimulation elicited a powerful relaxation of the longitudinal muscle of the rabbit portal vein in the presence of atropine and guanethidine, but not of the guinea-pig portal vein.2 Intramural nerve stimulation of the rabbit portal vein produced a 13 fold increase in release of (3)H-adenyl compounds after preloading with [(3)H]-adenosine. About 50% of this release was abolished by guanethidine. All release was abolished by tetrodotoxin. No significant release of radioactive compounds was observed during intramural nerve stimulation of the guinea-pig portal vein in the presence of guanethidine, although there was a 6 fold increase in release of radioactivity in the absence of drugs.3 Histochemical studies using quinacrine, which binds ATP showed a fine fluorescent nerve plexus, nerve bundles, and ganglion cells in the rabbit portal vein, but not in the guinea-pig portal vein. This plexus was still present after chemical sympathectomy with 6-hydroxydopamine.4 Adenosine 5'-triphosphate (ATP) relaxed the rabbit portal vein, but usually produced a biphasic response, consisting of a contraction followed by a relaxation, of the guinea-pig portal vein.5 Prostaglandins E(1) and E(2) caused contraction of the rabbit portal vein. Indomethacin, a prostaglandin synthesis inhibitor, potentiated the relaxations of the rabbit portal vein produced by both non-adrenergic, non-cholinergic nerve stimulation and ATP.6 High concentrations of antazoline and phentolamine, which antagonize purinergic responses in the guinea-pig taenia coli, caused a loss of basal tone so that it was not possible to assess their effects on the responses of the portal vein to either non-adrenergic, non-cholinergic nerve stimulation, or ATP.7 Comparison of the results on the portal vein of the rabbit and guinea-pig provides support for the view that: (i) quinacrine fluorescence can be used to localize purinergic nerves and that the rabbit portal vein is supplied by these nerves; (ii) ATP is released from adrenergic nerve fibres, although, based on histochemical analysis, about 3 to 7 times less than is released from purinergic nerve fibres.
Topics: Animals; Catecholamines; Cholinesterases; Electric Stimulation; Female; Guinea Pigs; Histocytochemistry; In Vitro Techniques; Male; Portal Vein; Purines; Quinacrine; Rabbits; Species Specificity; Sympathomimetics
PubMed: 427314
DOI: 10.1111/j.1476-5381.1979.tb07841.x -
British Journal of Pharmacology Feb 19781 The responses of the guinea-pig taenia coli, urinary bladder, and the rabbit portal vein to ultraviolet (u.v.) light were compared to those elicited by purinergic... (Comparative Study)
Comparative Study
1 The responses of the guinea-pig taenia coli, urinary bladder, and the rabbit portal vein to ultraviolet (u.v.) light were compared to those elicited by purinergic nerve stimulation and exogenous adenosine triphosphate (ATP).2 In the presence of sodium nitrite, u.v. light between 340-380 nm produced a maximum relaxation of the taenia coli. The relaxation was reversible and fast in onset. It was unaffected by atropine, guanethidine or low concentrations of phentolamine or propranolol. When the tone was low, the relaxation was usually followed by a ;rebound contraction' upon cessation of stimulation. Thus, the response to u.v. light closely resembles the responses to both purinergic nerve stimulation and exogenously applied ATP.3 U.v. light did not initiate impulses in purinergic nerves since its action was unaffected by tetrodotoxin; nor did it release ATP from nerve terminals (in contrast to its release during purinergic nerve stimulation). The adenosine-uptake inhibitor, dipyridamole, which potentiates the responses to purinergic nerve stimulation and ATP, did not affect the response to u.v. light.4 Agents known to alter postjunctional responses to purinergic nerve stimulation and ATP also altered the response to u.v. light. High concentrations of the 2-substituted imidazoline compounds, antazoline and phentolamine, which antagonize the responses to purinergic nerve stimulation and ATP, reduced the responses to u.v. irradiation. The prostaglandin synthesis inhibitor, indomethacin, which abolishes the ;rebound contraction' following stimulation of purinergic nerves, also blocks the ;rebound ;contraction' following u.v. irradiation. Increases in the K(+) concentration produced parallel changes in the inhibitory responses to u.v. light and purinergic nerve stimulation.5 U.v. light produced relaxation and inhibition of spontaneous activity of the rabbit portal vein (relaxed by ATP), but had no effect on the guinea-pig urinary bladder (contracted by ATP) and ureter (unaffected by ATP).6 It is suggested that u.v. light is acting on some part of the purinergic receptor complex which is involved in the mediation of inhibitory responses to ATP and purinergic nerve stimulation, and may therefore provide a way of investigating the chemistry of inhibitory purinergic receptors.
Topics: Animals; Colon; Electric Stimulation; Female; Guinea Pigs; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Nervous System Physiological Phenomena; Purines; Rabbits; Ultraviolet Rays
PubMed: 623941
DOI: 10.1111/j.1476-5381.1978.tb08459.x -
The Journal of Investigative Dermatology Jan 1950
Topics: Antazoline; Histamine; Humans
PubMed: 15402161
DOI: 10.1038/jid.1950.1 -
Biomedicine & Pharmacotherapy =... Jun 2024The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in...
The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.
Topics: Serum Albumin, Bovine; Molecular Docking Simulation; Histamine H1 Antagonists; Animals; Glycation End Products, Advanced; Glycosylation; Cattle; Receptors, Histamine H1
PubMed: 38663107
DOI: 10.1016/j.biopha.2024.116632 -
British Journal of Pharmacology Aug 19911. The patch clamp technique has been used to characterize the effects of phentolamine, an unselective blocker of alpha 1- and alpha 2-adrenoceptors, on the electrical...
1. The patch clamp technique has been used to characterize the effects of phentolamine, an unselective blocker of alpha 1- and alpha 2-adrenoceptors, on the electrical activity of isolated RINm5F insulin-secreting cells and the gating of ATP-regulated potassium (K+ATP) channels. 2. Current-clamp experiments carried out by use of both conventional whole-cell recordings and nystatin-perforated cells, have demonstrated that phentolamine (5-20 microM) in the complete absence of alpha-adrenoceptor agonists, caused a sharp depolarization of the cell membrane from approximately -66 mV to -42 mV. This depolarization was associated with the generation of calcium action potential-like spikes. In the continued presence of phentolamine, diazoxide (100 microM) reversed these effects by causing a hyperpolarization of the cell, thereby preventing Ca2+ spikes. 3. Unitary current events from K+ATP channels were recorded from both outside-out membrane patches and saponin permeabilized or open-cells. When added to either the inside or the outside of the plasma membrane, phentolamine (0.1-100 microM) blocked openings from these channels. The effects of phentolamine were rapid, sustained and fully reversible. Phentolamine was apparently a more effective blocker of channels from the inside than the outside of the membrane. 4. The KI value, corresponding to 50% inhibition of channels was estimated to be approximately 0.7 microM when phentolamine was added to the inside of the membrane and the Hill coefficient approximately 1. 5. Yohimbine (1-10 microM) and the chemically 2-substituted imidazoline alpha-adrenoceptor antagonists, antazoline (25 microM) and tolazoline (25 microM) were also found to block K+ATP channels in isolated patches of membrane. 6. In conclusion the present study demonstrates that phentolamine and other imidazoline adrenoceptor antagonists have effects upon ATP-sensitive K+ channels that are not associated with stimulation of the adrenoceptor.
Topics: Adenosine Triphosphate; Adrenergic alpha-Antagonists; Clone Cells; Phentolamine; Potassium Channels
PubMed: 1680516
DOI: 10.1111/j.1476-5381.1991.tb12340.x