Dipyridamole may be used safely in patients with ischaemic heart disease.

It is thought that up to 50% of patients with cerebrovascular disease will have concurrent ischaemic heart disease. Dipyridamole co-formulated with aspirin has been shown to increase the relative reduction in risk of second stroke in patients with prior stroke/transient ischaemic attack beyond that obtaining with aspirin alone. We have sought to resolve the question of whether dipyridamole treatment increases the risk of cardiac adverse events in patients with co-existing ischaemic heart disease.

The AMPA receptor/Na(+) channel blocker BIIR 561 CL is protective in a model of global cerebral ischaemia.

In this study, we investigated whether the novel neuroprotective compound dimethyl-[2-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-phenoxy]-ethyl]-amine hydrochloride, BIIR 561 CL, a combined non-competitive antagonist of AMPA receptors and blocker of voltage-gated Na+ channels, is protective in a rat model of severe global ischaemia. BIIR 561 CL administered immediately after 10 min of ischaemia (occlusion of both carotid arteries plus reduction of arterial blood pressure to 38-40 mm Hg) significantly reduced hippocampal damage at 4 x 26.8 mg/kg (subcutaneous injections).

In vivo pharmacology of BIIR 561 CL, a novel combined antagonist of AMPA receptors and voltage-dependent Na(+) channels.

Glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype and voltage-gated Na(+) channels are associated with diseases of the central nervous system characterized by neuronal over-excitation as in epilepsy or cerebral ischaemia. In animal models, AMPA receptor antagonists and Na(+) channel blockers provide protection in these conditions. Dimethyl-[2-[2-(3-phenyl-[1,2,4]oxadiazol-5-yl)-phenoxyl]-ethyl]-amine hydrochloride (BIIR 561 CL) combines both, AMPA receptor - and Na(+) channel blocking properties in one molecule.

Characterization of the anticonvulsant and neuroprotectant BIIR 561 CL in vitro: effects on native and recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors.

BIIR 561 CL is a novel blocker of AMPA receptors and voltage-dependent sodium channels. In this study we further describe the effects of BIIR 561 CL on AMPA receptor-mediated membrane currents in rodent neurons, as well as in cells expressing recombinant human GluR1/2 receptors in more detail. BIIR 561 CL suppressed responses to kainate in neuronal cultures from rat cortex with an IC50 of 9.

BIIR 561 CL: a novel combined antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors and voltage-dependent sodium channels with anticonvulsive and neuroprotective properties.

Antagonists of glutamate receptors of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) subtype, as well as of voltage-gated sodium channels, exhibit anticonvulsive and neuroprotective properties in vivo. One can postulate that a compound that combines both principles might be useful for the treatment of disorders of the central nervous system, like focal or global ischemia. Here, we present data on the effects of dimethyl-(2-[2-(3-phenyl-[1,2, 4]oxadiazol-5-yl)-phenoxy]ethyl)-amine hydrochloride (BIIR 561 CL) on neuronal AMPA receptors and voltage-dependent sodium channels.

Compensation of muscarinic bronchial effects of talsaclidine by concomitant sympathetic activation in guinea pigs.

The aim of the present investigation was to determine the reasons why the muscarinic receptor agonist talsaclidine (WAL 2014 FU, 1-azabicyclo[2.2.2] octane,3-(2-propynyloxy)-, (R)-,(E)-2-butenedioate) is devoid of bronchospastic effects in anaesthetized guinea pigs but causes contracture in isolated tracheal muscle from this species.

Hypotensive and bradycardic effects of talipexole (B-HT 920) in anaesthetized rabbits are antagonized by metoclopramide but not by yohimbine.

The interactions of talipexole (B-HT 920) and clonidine with selective alpha-adrenoceptor antagonists, yohimbine (alpha 2) and prazosin (alpha 1), as well as with dopamine receptor antagonists, metoclopramide (D2), domperidone (D2) and SCH23,390 (D1) were investigated in anaesthetized rabbits after i.v. administration.

Neuroendocrine and side effect profile of pramipexole, a new dopamine receptor agonist, in humans.

The effects and tolerability of pramipexole, a new dopamine D2-receptor agonist, on prolactin, human growth hormone, thyrotropin, cortisol, and corticotropin levels were investigated in a randomized, double-blind, crossover study in 12 healthy volunteers. Single oral doses of 0.1, 0.

Renal response to blood volume expansion in Brattleboro rats after acute treatment with vasopressin.

The renal response to iso-oncotic blood volume expansion with bovine serum albumin was studied in anaesthetized homozygous Brattleboro (DI) rats after acute (1 day) pretreatment with 1 U arginine-vasopressin (AVP) compared to heterozygous controls. In AVP-treated DI (DI + AVP) rats, basal urine flow as well as urinary sodium, chloride, and potassium excretion, were not different from controls. Diuresis and kaliuresis induced by volume expansion were blunted in DI + AVP rats.

Blood pressure lowering action and alpha-adrenolytic effect of adimolol in rats.

Adimolol is a new antihypertensive agent with strong nonselective beta- and moderate alpha-adrenolytic properties. In order to elucidate whether the alpha-adrenoceptor blockade by adimolol may contribute to the blood pressure lowering action of the compound, we tested 1) the effect on heart rate and blood pressure in conscious spontaneously hypertensive rats after oral administration and 2) the influence on the pressor effect of intra-arterially injected noradrenaline in autoperfused rat hindquarters after i.v.

Renal hyper-responsiveness to blood volume expansion in Brattleboro rats is not related to plasma ANF immunoreactivity.

1. Anaesthetized homozygous Brattleboro (DI) rats were used to study the renal response to iso-oncotic blood volume expansion. 2.

Hyperresponsiveness to atrial natriuretic factor in adult Brattleboro rats.

Renal and hemodynamic effects of an intravenous infusion of atrial natriuretic factor (ANF) (8 micrograms/h) were studied in homozygous Brattleboro rats, which lack endogenous vasopressin. Heterozygous rats were used as controls. ANF-induced increases in sodium, chloride and volume excretion were higher, whereas changes in potassium excretion were lower in homozygous, as compared to heterozygous rats.

Severe proteinuria without impairment of sodium and volume excretion after puromycin aminonucleoside administration in rats.

The effects of a single intravenous injection of 100 mg/kg puromycin aminonucleoside (PAN) on renal protein, electrolyte, and fluid excretion as well as inulin and lithium clearances in rats were investigated under basal conditions, after iso-oncotic blood volume expansion with bovine serum albumin (BSA) and during infusion of atrial natriuretic peptide (ANP). All treated rats developed severe proteinuria 7-28 days after injection. On day 17, the protein excretion of the PAN group was 1,050 +/- (SE) 118 micrograms/(min x kg body weight) compared with 42.

The binding of fluorescent 4,6,8(14)-triene-3-one steroids to cyclodextrins as a model for steroid-protein interactions.

The 4,6,8(14)-triene-3-one steroids, highly fluorescent in aqueous solutions, lose their fluorescence power when binding occurs to hydrophobic regions of other molecules, such as the hydrophobic cavity in the ring system of cyclodextrins. The fluorescence intensity decreases almost completely when beta- and gamma-cyclodextrins are present in the solution. Scatchard plots derived from fluorescence titrations show that one or two molecules of steroid bind to one cyclodextrin molecule with KD,F-values of about 10(-4)-10(-5) mol/liter.

Interactions of MEN 935 (adimolol), a long acting beta- and alpha-adrenolytic antihypertensive agent, with postsynaptic alpha-adrenoceptors in different isolated blood vessels--influence of angiotensin II.

MEN 935 [1-(3-[3-(1-naphthoxy)-2-hydroxypropyl) amino)-3,3-dimethylpropyl)-2-benzimidazolinone-hydrochloride monohydrate, adimolol] is a long acting antihypertensive agent with beta- and alpha-adrenolytic properties. Preliminary experiments in pithed rats had led to the suggestion that the alpha-adrenolytic activity was of the alpha 2-subtype. The alpha-adrenolytic properties of MEN 935 were now tested in isolated vascular preparations of rat aorta, rabbit vena ischiadica and rabbit vena cava inferior against the selective alpha 1-adrenergic agonist phenylephrine (PE) and the selective alpha 2-adrenergic agonist B-HT 920 [2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)azepine].

Fluorescence of 3-keto-steroids in aqueous solution. Probes for steroid-protein interactions.

The physiologically important 3-keto-steroids are non-fluorescent or only weakly fluorescent in protic as well as in aprotic solvents. In contrast, the 4,6,8(14)-triene-3-one steroids are highly fluorescent in aqueous solution but they do not appreciably fluoresce in other solvents. Evidence is presented that the introduction of double bonds into the skeleton of the 3-keto-steroids leads to a decrease of the energy of the lowest pi-pi* state, bringing this level into the neighbourhood of the non-fluorescent n-pi* state.

Atrial natriuretic factor.

Mammalian atria contain different peptides with potent diuretic, natriuretic, smooth muscle relaxing and blood pressure lowering properties. A preprohormone of these peptides is synthetized and stored in specific granules in atrial myocytes. Different peptides have been isolated, analyzed and in vitro synthetized.

Postjunctional alpha-adrenoceptors and influence of angiotensin II in different isolated blood vessels.

The effects of the selective alpha 1-and alpha 2-adrenergic agonists phenylephrine and B-HT 920 (2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo[4,5-d]azepine) and the respective antagonists prazosin and yohimbine on smooth muscle activity of isolated rat aorta, rabbit vena cava inferior and rabbit vena ischiadica have been investigated. In addition, the influence of angiotensin II on the effects of these agonists and antagonists was evaluated. Among the two agonists phenylephrine was the most potent in the rat aorta and B-HT 920 in the two venous vessels.