Neuroprotective efficacy of lifarizine (RS-87476) in a simplified rat survival model of 2 vessel occlusion.

1. A new, modified rat two vessel occlusion model (with hypotension) was established and the neuroprotective efficacy of the novel agent lifarizine (RS-87476) was examined. 2.

Reduction by lifarizine of the neuronal damage induced by cerebral ischaemia in rodents.

1. The objective of this study was to evaluate the broad neurocytoprotective potential of the novel sodium-calcium ion channel modulator, lifarizine (RS-87476), in two rodent 72 h survival models of forebrain ischaemia. 2.

The effect of lifarizine (RS-87476), a novel sodium and calcium channel modulator, on ischaemic dopamine depletion in the corpus striatum of the gerbil.

1. Unilateral ligation of the right common carotid artery in the anaesthetized gerbil for 3 h caused a 62.7% decrease in ipsilateral dopamine in the corpus striatum from 1.

Drugs acting on calcium channels: potential treatment for ischaemic stroke.

Calcium subserves a ubiquitous role in the organisation of cell function. Ca2+ channels which control influx may be modified in disease states. Animal models of cerebral ischaemia do present some problems when investigating potential therapies involving Ca2+ channels.

Prevention of myocardial enzyme release by ranolazine in a primate model of ischaemia with reperfusion.

In control anaesthetized baboons subjected to 30 min occlusion of the left anterior descending coronary artery, followed by 5.5 h reperfusion, total plasma levels for creatine kinase (CK) and lactate dehydrogenase (LDH) were markedly elevated in a time-related manner. In a second group of baboons pretreated 10 min prior to ischaemia with ranolazine [(+/-)-N-(2,6-dimethyl-phenyl)-4[2-hydroxy-3-(2-methoxyphenoxy)propyl]-1 - piperazine acetamide dihydrochloride; RS-43285-193] at 500 micrograms kg-1 i.

Effects of enprostil on cardiovascular and respiratory parameters in the dog, and on hematologic parameters in the rat, monkey, and human.

The effects of enprostil (+/-)-7-[(1R*,2R*,3R*)-3-hydroxy-2-[(E)-(3R*)-3-hydroxy-4-phenoxy-1- butenyl]-5-oxocyclopentyl]-4,5-heptadienoate) were studied on cardiovascular and respiratory parameters in the dog and on hematologic parameters in the rat, monkey, and human. Anesthetized dogs were instrumented to allow measurement of heart rate, systemic blood pressure, respiratory rate or tracheal pressure, and ventricular contractile force after intragastric (i.g.

A comparison of the effects of a series of anti-anginal agents in a novel canine model of transient myocardial ischaemia.

1. An anaesthetized canine model of transient myocardial ischemia (TMI) has been developed in which reproducible and reversible electrocardiographic (ECG) and haemodynamic responses are exacerbated by electrical pacing. 2.

Activators and inactivators of calcium channels: effects in the central nervous system.

The interactions of calcium antagonists or channel activators with the different classes of calcium channel are reviewed with particular emphasis on interactions with neuronal tissue; reasons for the failure of calcium antagonists to inhibit neurotransmitter release under normal circumstances are outlined. Calcium antagonists may be protective in several pathological situations and the possibilities of protection against ischaemic damage in the central nervous system are evaluated.

Effects of the novel class Ia and class III antiarrhythmic agent RS-87337 on myocardial conduction in the anaesthetised dog.

The effects of the novel Class Ia/III antiarrhythmic compound RS-87337 on canine myocardial conduction were compared with those of the Class I antiarrhythmic disopyramide. RS-87337 had no effects on intra-atrial (I-A) or intra-ventricular (I-V) conduction parameters up to 10 mg.kg-1 i.

Comparative protective effects of nicardipine, flunarizine, lidoflazine and nimodipine against ischaemic injury in the hippocampus of the Mongolian gerbil.

1. Morphological changes characterizing delayed neuronal death (DND) of selectively vulnerable CA1 pyramidal cells in the hippocampus of the Mongolian gerbil brain occurred 72 h after transient (5 min) bilateral occlusion of the common carotid arteries. 2.

The effects of the novel anti-anginal compound RS 43285 on myocardial conduction in the anaesthetized dog.

1. A pentobarbitone-anaesthetized canine model of myocardial conduction was developed to evaluate drug effects on intra-atrial (I-A), intra-ventricular (I-V) and atrioventricular (A-V) conduction parameters, both at rest and during electrical pacing of the right atrium or ventricle. Drug effects on the ability of the sino-atrial (SA) node to re-establish sinus rhythm on switching off electrical pacing were also considered.

The potential beneficial effect of nicardipine in a rat model of transient forebrain ischemia.

In a rat 3-day survival model of 10-minute four-vessel occlusion, halothane anesthesia was used to attenuate the ictal blood pressure elevation of the cerebral ischemic response and thereby maintain an isoelectric EEG. Selectively vulnerable regions of the brain were protected by preischemia plus postischemia maintenance treatment with the calcium entry blocker nicardipine. Compared with untreated animals, repeated doses at 500 micrograms/kg IP were markedly more effective than doses of 50 micrograms/kg.

Nicardipine in models of myocardial infarction.

In a dog model of partial myocardial ischaemia, superimposed ST segment elevations in epicardial ECGs were inhibited by nicardipine over a cumulative i.v. dose range of 1-20 micrograms kg-1.

The beneficial effect of nicardipine on the healing of myocardial infarcts in dogs.

The effect of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methyl amino)] ethyl ester 5-methyl ester hydrochloride (nicardipine, RS-69216, YC-93), on the healing of myocardial infarcts has been examined in dogs surviving for 3 months after ligation of the left anterior descending coronary artery (LAD). Three groups of 12-14 dogs were subjected to the following treatments: a) Group X received one-month oral pretreatment (1-2 mg/kg/d) with post-ligation i.v.

The gastrointestinal and autonomic effects of 3-methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide hydrochloride (tiquinamide).

3-Methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide hydrochloride (tiquinamide), a potent gastric anti-secretory compound, affords good protection against stress- and chemically-induced gastric and duodenal erosions. It causes a dose-related delay in gastric emptying and intestinal transit, and does not have a primary effect on gastric mucosal blood flow. The only actions of tiquinamide on the peripheral autonomic nervous system are weak, but apparently specific, histamine H2-receptor blocking activity, and non-competitive inhibition of acetylcholine and histamine responses at 10(-3) mol/l.

The gastric antisecretory activity of 3-methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide hydrochloride (tiquinamide).

3-Methyl-5,6,7,8-tetrahydroquinoline-8-thiocarboxamide hydrochloride (tiquinamide) possesses potent gastric antisecretory activity in a number of animal species. It causes a marked inhibition in the volume and concentration of basal and chemically-stimulated gastric acid secretion in the conscious rat and guinea-pig, and of chemically-stimulated secretion in the anaesthetised cat, dog and monkey. Marked activity is also seen in conscious Heidenhain-pouch dogs, against secretion stimulated by betazole and gastrin tetrapeptide.

The renin-angiotensin system, dietary salt, and increased sensitivity to noradrenaline in mesenteric vasculature preparations from renal/salt hypertensive rats.

Exogenous angiotensin II causes noradrenaline supersensitivity in rat mesenteric vasculature preparations. The noradrenaline supersensitivity of tissues from renal/salt hypertensive rats, with low plasma renin activity, is not caused by endogenous angiotensin II since it was unaffected by Sar1 Ileu8 angiotensin II. Dietary salt-loading caused a small increase in noradrenaline sensitivity.

The evaluation of the novel pressor activity of gamma-piperidinobutyramide (WY 20051, DF480).

1 gamma-Piperidinobutyramide (Wy 20051, DF480) injected intravenously evoked pressor responses in the anaesthetized ganglion blocked rat preparation over the dose range 2.4 x 10(-6)-3.0 x 10(-4) mol/kg.

Vascular reactivity to noradrenaline, potassium chloride, and angiotensin II in the rat perfused mesenteric vasculature preparation, during the development of renal hypertension.

The degree of reactivity to noradrenaline of the perfused mesenteric vasculature and the blood pressure of the renal hypertensive rat were correlated. Early (true) supersensitivity was demonstrated for noradrenaline and angiotensin but not for KCl. Later (apparent) hyperreactivity to all three substances was related to an elevated maximal response.