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M Dóda

Publications and source records attributed to M Dóda.

At least 19 recordsLinked to original sources
PubMed2003

A new short-acting non-depolarizing muscle relaxant (SZ1677) without cardiovascular side-effects.

BACKGROUND: In order to facilitate rapid tracheal intubation, the development of a rapid onset, short duration, non-depolarizing muscle relaxant without cardiovascular side-effects would be a significant accomplishment in the field of anesthesiology. The aim of the present study was to test the action of a new non-depolarizing muscle relaxant (SZ1677) on neuromuscular transmission, muscarinic (M2, M3) receptors and cardiovascular reactions and to compare it with clinically used muscle relaxants. METHODS: Neuromuscular transmission was studied by recording muscle contractions elicited by indirect electrical stimulation, using (i). in vitro isolated phrenic nerve-hemidiaphragm preparation of mice, rats and guinea pigs and (ii). in vivo sciatic nerve-anterior tibial muscle preparation of anesthetized rats, guinea pigs and cats. Cardiovascular effects of muscle relaxants were evaluated on the grounds of their effects on changes of blood pressure and heart rate induced by electrical stimulation of the right vagal nerve in anesthetized cats. To study postsynaptic antimuscarinic affinity of muscle relaxants on M3 receptors, oxotremorine-induced contractions of longitudinal muscle strip of guinea pig ileum were registered in their presence and absence. RESULTS: One of more than 120 newly synthesized non-depolarizing muscle relaxants compounds, 1-3[alpha-hydroxy-17beta-acetyloxy-2beta-(1,4-dioxa-8-azaspiro[4,5]dec-8-yl)-5alpha-androstane-16beta-il] -1-(2-propenyl)pyrrolidinium bromide (SZ1677), excelled with its advantageous pharmacological properties: relatively short duration of action, no accumulation and lack of unwanted side-effects. Pharmacodynamic studies show that SZ1677 is a non-depolarizing neuromuscular blocking agent with a relatively short duration and rapid onset of action in a variety of laboratory animal species. It is without cumulative effect, does not reduce blood pressure, and fails to produce tachycardia. Significant cardiac vagal blocking effects were not observed even at concentrations or dosages of 8 times the ED90. This compound, unlike many other muscle relaxants, does not have atropine-like effects on human atrial tissue; it does not increase the release of NA from sympathetic innervation in the heart. In all practical ways, at least from the vantage point of the preclinical study, SZ1677 compares favorably with all presently available short-acting muscle relaxants, including rapacuronium. CONCLUSION: In experiments, SZ1677 proved to be a short-acting neuromuscular blocking compound having a large safety margin between the doses required to produce neuromuscular block and those likely to lead to cardiovascular side-effects.

Androstanes↗
PubMed2000

Ischemic-like condition releases norepinephrine and purines from different sources in superfused rat spleen strips.

Transmitters and cotransmitters of the sympathetic nervous system are involved in the regulation of a variety of immune cell functions. However, it is not entirely clear what stimuli lead to the release of these molecules in immune organs. In this study, we investigated whether local ischemia can cause the parallel release of norepinephrine and its cotransmitter, ATP, in the spleen. Ischemic-like conditions, simulated by transient (15 min) O(2) and glucose deprivation, elicited a reversible increase in the release of both norepinephrine and purines from superfused spleen strips preloaded with [3H]norepinephrine or [3H]adenosine. HPLC analysis of the released tritium label revealed a net increase in the amount of ATP, ADP, AMP, adenosine, inosine, hypoxanthine and xanthine in response to ischemic-like condition. Selective O(2) or glucose deprivation, and Ca(2+)-free conditions differentially affected the outflow of [3H]norepinephrine and [3H]purines, indicating that they derived from different sources. The ABC transporter inhibitors glibenclamide (100 microM) and verapamil (100 microM) as well as low-temperature inhibited [3H]purine release evoked by ischemic-like conditions. Surgical denervation of the spleen reduced endogenous catecholamine content and [3H]norepinephrine uptake of the spleen, but not that of [3H]adenosine. In summary, these results demonstrate the release of norepinephrine and purines in response to an ischemic-like condition in an immune organ. Although both could provide an important source of extracellular catecholamines and purines involved at various levels of immunomodulation, the source and mechanism of norepinephrine and purine efflux seem different.

Adenine↗
PubMed1998

Coloured peptides: synthesis, properties and use in preparation of peptide sub-library kits.

Several methods were developed for the solid-phase synthesis (SPPS) of coloured peptides and peptide libraries. At first a bifunctional red compound, 4-(4-(N-ethyl-N-(3-(tert-butyloxycarbonyl)aminopropyl)amino)phenylazo)be nzoic acid (Boc-EPAB), was coupled with chloromethyl resin to obtain a new solid support suitable for SPPS using Boc chemistry. Peptides synthesized on this coloured resin had the chromophore at their C-termini. N-terminally coloured peptides were synthesized on a traditional solid support, coupled with chromophoric carboxylic acid before cleavage. A model pentapeptide, Phe-Ala-Val-Leu-Gly, and its ten derivatives were synthesized and their properties studied. It was found that the presence of chromophores decreases the water solubility of peptides. However, insertion of solubilizing tags (penta-lysine sequences or polyoxyethyl chains) into the molecule of any coloured derivative resulted in enhancement of the solubility. The RP-HPLC hydrophobicity indexes (phi0) of the coloured peptides were also determined because phi0 values are closely related to their water solubility. A coloured pentapeptide library was synthesized using the portioning-mixing method. Each component of this library contained the red azo dye (EPAB) and the penta-lysine tag. Before the last coupling step the samples were not mixed. All of the 19 sub-libraries obtained after cleavage were readily soluble in water, giving intense red solutions. The effect of chromophore (EPAB) and/or penta-lysine solubilizing tag on the biological activity was also studied. Potencies of the bovine neurotensin 8-13 fragment and its different coloured and penta-lysine derivatives were compared in isolated longitudinal muscle strips of guinea pig ileum. It was shown that the hexapeptide with penta-lysine tag had almost the same activity as the 8-13 fragment itself. The activity of the EPAB-derivative was found to be rather low. However, the presence of the solubilizing tag in the coloured hexapeptide compensated the negative effect of the chromophore.

Aminobenzoates↗
PubMed1998

Effect of bimoclomol (N-[2-hydroxy-3-(1-piperidinyl) propoxy]-3 pyridine-carboximidoyl-chloride) on iminodipropionitrile-induced central effects.

Dyskinesia is frequently seen in neurological disorders affecting the basal ganglia. Iminodipropionitrile (IDPN) produces a somewhat similar motor syndrome in rodents, one that is a possible model for dyskinesia. Because in previous studies the compound (N-[2-hydroxy-3-(1-piperidinyl) propoxy]-3 pyridine-carboximidoyl-chloride) (Bimoclomol, BRLP-42) was shown to provide protection against IDPN-induced retinopathy; we investigated the effect of BRLP-42 on IDPN-induced motor changes and on IDPN-induced cerebral amino acid level changes in rats and mice. IDPN had a biphasic effect on motor activity in C57BL/6 mice: it was a depressant for 24 days and a stimulant after 30 days. Bimoclomol inhibited the motor depressant effect and enhanced the stimulatory effect of IDPN in this mouse strain. In BALB/cBy mice and Sprague Dawley rats IDPN produced persistent vertical head movements and changes in the level of glutamic acid in brain. Bimoclomol reduced the effect of IDPN on head movements and blocked the effect on cerebral glutamate; by itself it had no effect on motor activity in either species. Bimoclomol inhibited ischemia-induced [3H]norepinephrine release from rat hippocampal slices. Our findings indicate that Bimoclomol could have a beneficial effect on some dyskinesias, and on drug-induced vertical head movements.

Animals↗
PubMed1997

Role of different subtypes of adrenoceptors in pressor responses to catecholamines released from sympathetic nerve endings.

The role of alpha 1- and alpha 2-adrenoceptors in the vascular effects of catecholamines, either released locally from sympathetic nerve endings (e.g., in vascular smooth muscle) or derived from the adrenal medulla or administered intravenously, was studied using selective antagonists of these adrenoceptors. The ganglionic stimulant dimethylphenyl-piperazinium-iodide (DMPP) exerted dual actions on blood pressure: a rapid and short-term pressor reaction (phase I) resulting from catecholamine release elicited by ganglion stimulation, followed by a more sustained blood pressure elevation (phase II) resulting from the circulating catecholamines released from the adrenal medulla. The selective alpha 2-adrenoceptor, but a not subtype selective, antagonist 7,8-(methylenedioxi)-14-alpha-alloberbane HCl (CH-38083) (50-100 micrograms/kg, IV) significantly (p < 0.05) inhibited the pressor effects of epinephrine and norepinephrine given intravenously and phase II of the DMPP-induced pressor reaction. Idazoxan exerted similar effects, but at higher doses (400-600 micrograms/kg, IV). WB-4101 (50-100 micrograms/kg, IV) and BRL-44408 (2-3 mg/kg, IV), two selective alpha 2A-adrenoceptor antagonists, had the same activity as CH-38083, except did not inhibit the pressor effect of intravenously administered norepinephrine. The alpha 2B-adrenoceptor selective antagonist, ARC-239 (150 micrograms/kg, IV) did not influence phase II of DMPP-induced pressor reaction. Prazosin (200 micrograms/kg, IV), an antagonist of alpha 1 and alpha 2B-adrenoceptors, reduced blood pressure, the pressor response to intravenously administered epinephrine, and phase I of the DMPP-induced pressor effect. In addition, it completely inhibited the pressor responses to DMPP remaining after administration of CH-38083. These results suggest that the postsynaptically located alpha 1- and alpha 2(A and B)-adrenoceptors are involved in pressor response to norepinephrine and epinephrine, and are sensitive and accessible to catecholamines released locally from the axon terminals, and from the circulation to a different extent. These results may have great therapeutical importance in hypertension, for which the involvement of both a high level of circulating and locally released catecholamines may be indicative of the usefullness of a combination (alpha 1- and alpha 2-adrenoceptors- and Ca-channel-blocking agents) therapy.

Adrenergic alpha-Antagonists↗
PubMed1989

Effect of CH-38083, a selective antagonist of alpha 2-adrenoceptors, on renal sympathetic function.

The effects of 7,8-(methylenedioxi)-14-alpha-hydroxyalloberbane HCl (CH-38083), a structurally new, selective and potent alpha 2-adrenoceptor antagonist, and of idazoxan, were studied on both the spontaneous activity of the postganglionic sympathetic renal nerve and on the clonidine- or xylazine-induced inhibitory action in anaesthetized cats. The drug CH-38083 (30-200 micrograms/kg, i.v.) caused a sustained increase of the sympathetic activity and blood pressure. Larger doses of idazoxan (200-500 micrograms/kg, i.v.) were needed to induce similar effects. Both antagonists were effective in antagonizing the sympatho-inhibitory effect of clonidine or xylazine. The excitatory response to selective alpha 2-adrenoceptor antagonists suggests that the sympathetic output undergoes tonic inhibition due to a permanent alpha 2-adrenoceptor stimulation.

Adrenergic alpha-Antagonists↗
PubMed1989

Interactions of apomorphine and a novel neuroleptic dibenzodioxazocine derivative, as evidenced by changes of somato-autonomic reflexes and spontaneous sympathetic activity in cats.

The apomorphine-antagonistic effects of EGYT-2509, a novel neuroleptic compound, has been studied by two different methods suitable for investigating the dopaminergic modulation of sympathetic output. (1) In cats lightly anaesthetized with urethane (600 mg kg-1 i.p.), blood pressure (BP) reflexes evoked by electrical stimulation of the sciatic nerve were inhibited by apomorphine (0.2 mg kg-1 i.v.) at low frequencies of stimuli (2-8 Hz), while the BP reflexes were facilitated by apomorphine at higher frequencies of stimulation; the evoked contractions of the nictitating membrane were depressed in the entire range of frequencies applied. EGYT-2509 (1.5 mg kg-1 i.v.) antagonized both the inhibition and facilitation of pressor reflexes induced by apomorphine. EGYT-2509, given alone, in doses exceeding 1.5 mg kg-1 either did not influence or inhibited the responses of nictitating membrane and of BP; the inhibition could be antagonized by haloperidol. The apomorphine-induced sustained hypotension was inhibited by EGYT-2509 (18.5 mg kg-1): after EGYT-2509, higher doses of apomorphine (0.7 vs 0.2 mg kg-1) were required for the effect. Sustained hypotension could be elicited by EGYT-2509, too; after apomorphine, smaller doses of EGYT-2509 (8.5 vs 18.5 mg kg-1) were enough to decrease BP. (2) In cats anaesthetized with chloralose and urethane (50 and 400 mg kg-1 i.p., respectively), apomorphine (0.2 mg kg-1) inhibited the spontaneous activity of the postganglionic renal sympathetic nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Synthesis and pharmacological evaluation of some new tetrahydroisoquinoline derivatives inhibiting dopamine uptake and/or possessing a dopaminomimetic property.

As shown by structure-activity relationship studies in 8-(substituted-amino)-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines, the most important structural requirement for a marked antidepressant action is the presence of an ureido, (alkoxycarbonyl)amino, or [(alkylamino)acyl]amino group attached to the isoquinoline skeleton in position 8. In one of the biological tests a significant difference was found between 8-amino-4-phenyl-2-methyl-1,2,3,4-tetrahydroisoquinoline (nomifensine) and the new compounds synthesized. Nearly all compounds substituted in the amino group either decrease the spontaneous motility in mice or exert no effect on it. Two syntheses have been elaborated for the preparation of the compounds represented by the general formulas II-V where R1 = hydrogen, halogen, or methyl; Y = CONHR, OCOR, or CO(CH2)nNHR, in which R = alkyl or aralkyl or NHR = cyclic amine and n = 1-2. The syntheses start either from the corresponding 8-amino-4-aryl-2-methyl-1,2,3,4-tetrahydroisoquinolines or from the corresponding noncyclized amino alcohols. Of the compounds, 4-(p-chlorophenyl)-8-[(ethoxy-carbonyl)amino]-2-methyl-1,2,3,4- tetrahydroisoquinoline was found to possess the highest activity.

Animals↗
PubMed1985

The effect of dopamine, apomorphine and piribedil on the mesenterial blood flow of the cat.

Responses to i.v. administration of dopamine, apomorphine, piribedil and bromocriptine were investigated in the feline mesenteric vascular bed. Dopamine increases the mesenterial flow in doses of 0.3 to 30 micrograms/kg; its effect can be inhibited by 1 to 3 mg/kg of sulpiride. Apomorphine and piribedil also increased the blood flow, but only in 20 to 200 times higher doses; they show a tachyphylaxis phenomenon and their maximal activity is 32 and 59 per cent, respectively, that of dopamine. Apomorphine is a partial agonist of dopamine and can inhibit the activity of the transmitter amine. Bromocriptine has no activity on the feline mesenterial flow. The postsynaptic dopamine receptors of the cat can be characterized by the following: strong efficacy of dopamine and lower ones of apomorphine, piribedil and of sulpiride. The presynaptic dopamine receptors are involved mostly in the hypotension, they are activated by low doses of apomorphine, and piribedil and by higher doses of dopamine; sulpiride reacts with these receptors in much lower doses than with the postsynaptic ones.

Animals↗
PubMed1983

The inhibitory effect of dopaminomimetics on nerve stimulation-induced vasoconstriction of the cat's carotid artery.

The experiments were carried out in cats anaesthetized with chloralose and urethane. The preganglionic sympathetic nerve was stimulated and blood flow in the common carotid artery and the contractions of the nictitating membrane were recorded. Three intravenously given dopaminomimetics inhibited the vasoconstriction and nictitating membrane contractions induced by nerve stimulation. The rank order of the drugs was: bromocriptine greater than apomorphine greater than piribedil. The relative potencies on carotid blood flow were 100:30:3.1, respectively. The presynaptic site of activity was discussed.

Animals↗
PubMed1982

Effects of dopaminergic agonists on somato-autonomic reflexes.

In cats lightly anesthetized with urethane (600 mg/kg, i.p.) reflexes of the blood pressure (BP) and of the nictitating membrane (NM) were elicited by stimulation of the sciatic nerve (16 V, 0.3 ms, 1-128 Hz, 2 s or 2 min) prior to and after the administration of apomorphine (0.05-0.2 mg/kg, i.v.) or piribedil (0.4-1.0 mg/kg, i.v.). In case of short-train (2 s) stimulation, both dopaminergic agonists shifted the frequency-response curves of NM contractions to the right, i.e. depressed NM reflexes in the entire range of the stimulation frequencies applied. At the same time, BP reflexes were depressed only in the range of lower frequencies (1-4 Hz). At higher rates (32-128 Hz) BP reflexes were potentiated. The reactions of BP to sustained (2 min) stimulations displayed a flat pressor plateau in response to lower-frequency stimulation, and a two-component pattern (an initial pressor peak followed by a plateau) to the higher-frequency one. Compatibility with the effects seen to short-train stimulations, the dopaminergic agonists prolonged the rise-time and augmented the amplitude of the initial pressor peak to sustained stimulations with lower and higher frequencies, respectively. The plateau of the pressor response to higher frequencies was depressed by higher doses (greater than 0.4 mg/kg) of piribedil. Administration of haloperidol (0.05-0.2 mg/kg, i.v.) resulted only in a partial restoration of the reflexes of BP and NM. The manifold effects of dopaminergic agonists on the somato-autonomic reflexes studied support the thought than NM and BP reflexes are organized, at least partially, in different ways.

Animals↗
PubMed1981

Influence of the dopaminergic agonists bromocriptine, piribedil and nomifensine on the sympathetic neural transmission in the nictitating membrane of the cat.

The effect of some dopaminergic drugs on the nictitating membrane contractions induced by cervical sympathetic nerve stimulation was investigated in cats. Bromocriptine and piribedil injected into the lingual artery inhibited the nerve stimulation-induced contractions but did not suppress the effect of noradrenaline. Both compounds caused a parallel shift of the frequency-effect curve to the right. Nomifensine (in high doses, after desipramine pretreatment) inhibited the contractions induced both by nerve stimulation and by noradrenaline. Haloperidol or sulpiride antagonized the inhibition due to piribedil. Sulpiride prevented the effect of bromocriptine. We suppose that these agonists have a specific inhibitory activity on the presynaptic dopaminergic receptors.

Animals↗
PubMed1981

The influence of dopamine and dopaminergic agonists on the contractions of field stimulated rat vas deferens.

In isolated field stimulated rat vas deferens frequency-response curves were shifted to the right by noradrenaline, dopamine, apomorphine, bromocriptine and nomifensine. Piribedil was found to be inactive. Phentolamine antagonized the effect of each active drug. The inhibition due to dopamine and apomorphine was also counteracted by haloperidol and sulpiride, while that caused by bromocriptine and nomifensine only by sulpiride. On the basis of these results an interaction was suggested between the presynaptic alpha and dopaminergic receptors: in the rat vas deferens dopaminergic receptors might activate alpha 2 receptors. The agonists increased the slope of the frequency-response curves. The drugs had a reversible activity on the vas deferens, except for bromocriptine which could not be removed by repeated wash-outs from the organ.

Animals↗
PubMed1981

Influence of dopamine and dopaminergic agonists on relaxation of isolated rabbit ileum induced by sympathetic nerve stimulation.

The inhibitory effect of noradrenaline, dopamine and four dopaminergic agonists on smooth muscle relaxation induced by nerve stimulation was compared in isolated rabbit ileum. All these compounds inhibit the relaxation evoked by nerve stimulation. Their activity decreased in the following order: bromocriptine, noradrenaline, nomifensine, dopamine, piribedil and apomorphine. Yohimbine inhibited the effect of noradrenaline and to a lesser extent that of dopamine, while the antidopamine agent sulpiride abolished the effect of dopamine, apomorphine and nomifensine. The presynaptic action of these compounds is discussed.

Animals↗
PubMed1978

Effects of phenytoin on sympathetic reflex responses in the cat.

Phenytoin (DPH), in a low dose (2 mg/kg) was found to potentiate reflex elevations in blood pressure and responses of the nictitating membrane induced either by the electrical stimulation of the sciatic nerve or by intravenously applied pentetrazol in light anaesthetized cats. Pressor responses to carotid occlusion under chloralose anaesthesia were also potentiated. In contrast a high dose (20 mg/kg) of DPH exerted an inhibitory effect on these responses. These effects of DPH on sympathetic reflex responses proved to be long-lasting. Intravenously applied picrotoxin (0.05 mg/kg) or the same dose of ouabain, injected into the vertebral artery, partially reversed the inhibitory effect of DPH (20 mg/kg). Our data support the suggestion that DPH exerts its inhibitory action by effecting ionic fluxes in the CNS, mostly in inhibitory structures.

Animals↗
PubMed1978

Influence of intraventricularly applied apomorphine on somato-vegetative reflexes in cats.

To obtain information about the dopaminergic neurotransmission processes taking part in the somatovegetative reflexes the effects of intraventricularly given apomorphine were studied in lightly anaesthetized cats. The level of blood pressure and the reflexogenic hypertension due to central sciatic nerve stimulation were not changed when apomorphine was applied into the lateral and third but was inhibited when given into the fourth ventricle. The nictitating membrane contractions elicited by sciatic nerve stimulation were inhibited by apomorphine when introduced into each part of the ventricular system. Thus the inhibitory dopaminergic synapses located in the structures lining the walls of the brain ventricular system reached by apomorphine appear to be involved in the central control of somato-vegetative reflexes.

Animals↗
PubMed1978

The effects of intraventricularly administered GABA and picrotoxin and their interactions on somato-vegetative reflexes in cats.

The effects of intraventricularly (third, fourth and lateral cerebral ventricles) applied GABA and picrotoxin on blood pressure and reflexogenic hypertension and nictitating membrane contractions after central sciatic nerve stimulation were studied in lightly anaesthetized cats. The interactions between both substances were also studied. It was shown that picrotoxin caused a strong elevation of blood pressure and a long lasting contraction of the nictitating membrane when infused into each part of the cerebral ventricular system. These effects of picrotoxin were antagonized by GABA. GABA inhibited the reflexogenic hypertension when given into the fourth ventricle and the reflexogenic nictitating membrane contractions given into the third and fourth ventricles. Picrotoxin antagonized the inhibitory effects of GABA on the reflexogenic nictitating membrane contractions. It is concluded that in the central regulation of some somato-vegetative reflexes the GABA-ergic transmitter system takes part.

Aminobutyrates↗