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Biomedical subjects

J Maj

Publications and source records attributed to J Maj.

At least 217 records · Page 12Linked to original sources
PubMedDate not supplied

Central action of Craviten (M-71).

Craviten (M-71) or 2S, 2'S) N, N'-dimethyl-N, N'-bis [1-(3', 4', 5' -trimethoxy-benzoyloxy)-butyl-2]-ethylenediamine dihydrochloride an agent with a strong antiarrhythmic action has practically no effect on the central nervous system of rats and mice. It exerts no effect on the spontaneous motor activity, on amphetamine-stimulated hyperactivity, on rota-red performance, it has no analgesic and anticonvulsant action and does not change the hexobarbital sleeping time. No effects of Craviten were observed on the body temperature in rats and mice. It decreased the arterial blood pressure in rats and stimulated slightly respiration. The hypotensive effect was dose-dependent. The LD50 of the preparation is: rats: 142 mg/kg ip, 15 x 8 mg/kg iv; mice: 550 mg/kg ip; rabbits: 5 x 1 mg/kg iv.

Amphetamine↗
PubMedDate not supplied

Pharmacological properties of Craviten (M-71).

The preparation Craviten (M-71) produced by POLFA Pharmaceutical Works in Cracow (2S, 2'S) N, N'-dimethyl-N, N'-bis-[1-(3',4',5'-trimethoxybenzoyloxy)-butyl]-2-ethylenediamine dihydrochloride) prevents and abolishes heart rhythm disturbance induced in the rat with BaCl2, CaCl2, adrenaline or aconitine. The doses effectively preventing arrhythmia development were in the range from 0.035 to 0.175 mg/kg. They are many times lower than the doses of lidocaine, hexobendine, procaine amide and D,L-propranolol producing a similar effect. Craviten has a much more favourable therapeutic index than these antiarrhythmic agents. Craviten causes sinus bradycardia and slows down myocardial conduction. It exerts a spasmolytic effect about 70 times as strong as papaverine. It has no influence on the central nervous system, on urine excretion, and after topical application it has no irritating or local anaesthetic effect. The 2R, 2'R isomer of Craviten has a similar profile of pharmacological action but its antiarrhythmic and spasmolytic effects are many times weaker.

Animals↗
PubMedDate not supplied

Central action of mepiprazole.

Mepiprazole, a phenylpiperazine derivative, strongly antagonizes the behavioral syndromes evolved by 5-hydroxytrypotophan. The drug did not affect the serotonin neurons in the preparation of flexor reflex of the hind paw of the spinal rat: in higher doses it depressed the reflex showing noradrenolytic properties. Mepiprazole antagonized the fenfluramine-induced hyperthermia, depressed spontaneous locomotor activity, produce hypothermia and was inactive in the despair test. The results suggest that mepiprazol may have noradenolytic properties; its possible influence on the serotonergic system is masked by noradrenolytic properties and hence difficult to demonstrate.

Animals↗
PubMedDate not supplied

Central serotoninmimetic action of phenylpiperazines.

Studies of 1-(m-chlorophenyl)-piperazine (m-CPP), 1-(p-chlorophenyl)-piperazine (p-CPP) and 1-phenylpiperazine (PP) were carried out on rats, mice and rabbits in order to assess their stimulatory effect on the central serotonin system. It was found out that m-CPP and p-CPP evoked a characteristic syndrome in the mouse behavior. All the phenylpiperazine derivatives stimulated the flexor reflex in the spinal rat and evoked hyperthermia in rats at a high ambient temperature (28 degrees C) and in rabbits. The above effects were abolished by cyproheptadine, a drug blocking the serotonin receptors. The obtained results indicate that the phenylpiperazine derivatives studied have a central serotoninmimetic action.

Animals↗
PubMedDate not supplied

Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, in mice.

Central effects of CGP 37849 and CGP 39551, competitive NMDA receptor antagonists, were studied in male Albino-Swiss mice. CGP 37849--at high doses only--increased the locomotor activity, while CGP 39551 decreased it. CGP 37849 and CGP 39551 did not change the locomotor activity, in monoamine-depleted mice (treated with reserpine + alpha-methyltyrosine). However, when administered together with clonidine, both those compounds produced a distinct hyperactivity. That antiakinetic effect was antagonized by haloperidol, but not by prazosin or idazoxan. In monoamine-depleted mice both the CGP compounds inhibited the locomotor hyperactivity evoked by apomorphine or L-DOPA (given jointly with benserazide). CGP 37849 antagonized the catalepsy evoked by fluphenazine, haloperidol, spiperone and reserpine. After CGP 39551 administration, a decreased muscle tension was observed, which rendered evaluation of the influence on catalepsy impossible. The obtained results (the antiakinetic effect, antagonized by haloperidol, and the anticataleptic effect) indicate that the NMDA receptor antagonists studied may act via an indirect activation of the dopamine system.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Central effects of repeated treatment with CGP 37849, a competitive NMDA receptor antagonist with potential antidepressant activity.

CGP 37849, a competitive NMDA receptor antagonist, was administered repeatedly (10 mg/kg po, twice daily for 14 days) to male Wistar rats. In behavioral studies it did not affect the locomotor activity, but enhanced the d-amphetamine-induced hyperactivity. Biochemical studies of the concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), noradrenaline (NA), 5-hydroxytryptamine (5-HT) and 5-hydroxyindole acetic acid (5-HIAA) in the rat cerebral cortex, striatum and nucleus accumbens showed that only the concentrations of DOPAC (an increase) and NA (a decrease) were changed in the nucleus accumbens. Repeated administration of CGP 37849 increased the density of dopamine D1 receptors labelled with [3H]-SCH 23390 in the rat striatum, but not in the limbic forebrain, having exerted no effect on the density of D2 receptors labelled with [3H]-spiperone. The density of alpha 1- and beta-adrenoceptors, labelled with [3H]-prazosin and [3H]-dihydroalprenolol, respectively, were unchanged in the cerebral cortex. The obtained results indicate that in some experimental paradigms CGP 37849 given repeatedly produces effects similar to those of typical antidepressant drugs.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex.

Central effects of SL 82.0715, an antagonist of polyamine site of the NMDA receptor complex, was studied in male Albino-Swiss mice. SL 82.0715, in doses which given alone were inactive in electroshock-induced seizures, potentiated the anticonvulsant effects of CGP 37849. In normal mice, SL 82.0715 decreased the spontaneous locomotor activity, did not affect the locomotor hyperactivity induced by MK-801 and attenuated CGP 37849-induced locomotor hyperactivity. The D-amphetamine locomotor hyperactivity was also antagonized by SL 82.0715. SL 82.0715 did not significantly change the locomotor activity in monoamine-depleted mice (treated with reserpine + alpha-methyl-p-tyrosine). When administered together with clonidine, SL 82.0715 increased the locomotor activity in monoamine-depleted mice but this effect did not reach the level of statistical significance. SL 82.0715 did not change the locomotor activity induced by joint administration of clonidine and MK-801 or clonidine and CGP 37849, in monoamine-depleted mice. The locomotor hyperactivity evoked by L-DOPA (given jointly with benserazide) was not changed by SL 82.0715. SL 82.0715 had no effect on fluphenazine- and haloperidol-induced catalepsy in mice. CGP 37849 attenuated catalepsy induced by haloperidol; that effect was not changed by SL 82.075. The studied compound did not affect the immobility time and had no effect on the action of MK-801 or CGP 37849 in the forced swimming test. The obtained results indicate that SL 82.0715 has a different pharmacological profile than other NMDA antagonists (at least MK-801 and CGP 37849). SL 82.0715 does not increase behavioral actions of MK-801 and CGP 37849, potentiating anticonvulsant effect of CGP 37849 only.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

Some central effects of kynurenic acid, 7-chlorokynurenic acid and 5,7- dichloro-kynurenic acid, glycine site antagonists.

Strychnine-insensitive glycine site is one of a few binding sites of NMDA receptor complex. The aim of these study was to find out whether compounds regarded as glycine antagonists-kynurenic acid (KA), 7-chlorokynurenic acid (7-CKA), 5,7-dichlorokynurenic acid (5,7-DCKA) evoke the effects analogous to those of the NMDA receptor antagonist, CGP 37849 (or MK-801) and/or can modulate the effects of the last compounds in rats. KA (but not 7-CKA, given ip) inhibited electroshock-induced seizures and increased the anticonvulsant effect of CGP 37849. CGP 37849-induced locomotor hyperactivity was enhanced by KA, 7-CKA (icv but not ip) and 5,7-DCKA. D-Amphetamine-induced hyperactivity was inhibited by KA as well as 7-CKA. In monoamine-depleted rats 7-CKA (but not KA) increased the antiakinetic effect of clonidine; the antiakinetic effect of L-DOPA was enhanced by 7-CKA and 5,7-DCKA, but not by KA. KA and 7-CKA did not change the spiperone-induced catalepsy but they attenuated the anticataleptic effect of CGP 37849; the studied drugs did not change the anticataleptic effect of MK-801. 7-CKA given icv did not influence the spiperone-induced catalepsy as well as the anticataleptic effect of CGP 37849. In the forced swimming test KA, given once, prolonged (50 mg/kg) or did not change (200 and 300 mg/kg) the immobility time. 7-CKA did not affect the immobility time in this model. When given three times KA (200 mg/kg) and 7-CKA (20 mg/kg) reduced the immobility time; the lower doses of KA and 7-CKA prolonged or did not change the immobility time, respectively. Joint injection with imipramine and KA (or 7-CKA) induced the decrease of immobility time (vs imipramine alone or glycine antagonist alone); in the case of joint injection with citalopram + KA (or 7-CKA), the time of immobility was prolonged or not changed. In conclusion, the obtained results point to similarities between glycine antagonists (kynurenine derivatives) and CGP 37849 and to the possibility of positive cooperation between the NMDA- and glycine-sites antagonists.

Amphetamine↗
PubMedDate not supplied

The effect of repeated treatment with oxaprotiline enantiomers on central 5-HT receptor subpopulations.

The effect of repeated administration of (+)-OXA (a noradrenaline (NA) uptake inhibitor) and (-)-OXA (devoid of an effect on the NA uptake, but a clinically active antidepressant drug) on central 5-HT receptor subpopulations was studied. (-)-OXA given repeatedly, but not acutely, attenuated the 8-OH-DPAT-induced hypothermia in mice. (+)-OXA administered acutely, as well as repeatedly, was inactive in that test. The 8-OH-DPAT-induced syndrome in rats was attenuated by both OXA isomers administered either acutely or repeatedly. The hypothermia induced by m-CPP in mice was attenuated by single-dose administration of (+)-OXA and (-)-OXA; when given repeatedly, (+)-OXA increased the action of m-CPP. (-)-OXA administered repeatedly was inactive in that test. Either single or repeated administration of (+)-OXA had practically no effect on the depression of exploratory activity induced by m-CPP. (-)-OXA administered acutely or repeatedly attenuated the effect of m-CPP in the same manner. Acute, but not chronic, administration of (-)-OXA reduced the number of head-twitch episodes induced by 5-HTP in mice. Repeated, but not acute, treatment with (+)-OXA attenuated the effect of 5-HTP. The obtained results indicate that (+)-OXA administered repeatedly increases the reactivity of 5-HT1B receptors, decreases the reactivity of 5-HT2 receptors, and has no effect on the reactivity of 5-HT1A- (pre- and postsynaptic) and 5-HT1C-receptors. (-)-OXA given repeatedly decreases the reactivity of presynaptic 5-HT1A receptors and has no influence on the reactivity of postsynaptic 5-HT1A-, 5-HT1B-, 5-HT1C- and 5-HT2-receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Sedative action of low doses of dopaminergic agents.

The activity of rats receiving low doses of dopaminergic agonists and neuroleptics was tested in the "open-field" test. Apomorphine, piribedil, L-DOPA, and nomifensine given at low doses (1-500 mug/ig) depressed the activity of animals. Spiperone and chlorpromazine given at low doses increased the activity, particularly in respect of one of the parameters investigated: the time of walking. Low doses of pimozide, haloperidol, and fluphenazine did not affect measurably the animal behavior. Spiperone counteracted the sedation induced by low doses of apomorphine, piribedil, and nomifensine. Chlorpromazine prevented the sedation produced by apomorphine. In the rats with a lesion of the substantia nigra only nomifensine retained its sedative action, while apomorphine and piribedil ceased to produce it. The reported results further support the hypothesis about the existence and the role of dopaminergic autoreceptors.

Animals↗
PubMedDate not supplied

Some behavioral effects of CNQX AND NBQX, AMPA receptor antagonists.

CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) and NBQX (2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline), two competitive AMPA (non-NMDA glutamate) receptor antagonists, as well as their interaction with CGP 37849, a competitive NMDA receptor antagonist, were studied in rats and mice. CNQX and NBQX inhibited the locomotor activity of naive rats. No symptoms of behavioral excitation were observed. CGP 37849 induced locomotor hyperactivity which was reduced by CNQX and NBQX. In monoamine-depleted rats (pretreated with reserpine + alpha-methyl-p-tyrosine), none of the two quinoxalines nor CGP 37849 antagonized akinesia. The antiakinetic effect of L-DOPA was increased by CGP 37849, but not by CNQX or NBQX. The latter action of CGP 37849 was decreased by CNQX and NBQX. The antiakinetic effect of clonidine was not changed by CNQX. The locomotor hyperactivity induced by apomorphine or cocaine was not modified by CNQX. Neither of the quinoxalines changed the catalepsy induced by haloperidol or spiperone. The fluphenazine catalepsy was slightly decreased by CNQX and increased by NBQX. CNQX and NBQX were inactive in the forced swimming test; CNQX (but not NBQX) increased the CGP 37849-induced reduction of the immobility time. CNQX decreased the muscle tone of hind limbs in naive and monoamine-depleted rats. The obtained results indicate that the AMPA receptor antagonists differ in their neuropharmacological profile from CGP 37849, an NMDA receptor antagonist. There is no positive cooperation (except for the forced swimming test) between NMDA and AMPA receptor antagonists; on the contrary, an antagonistic between them has been observed.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMedDate not supplied

Some central effects of GYKI 52466, a non-competitive AMPA receptor antagonist.

GYKI 52466 [1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine] has been described as a non-competitive AMPA (non-NMDA glutamate) receptor antagonist. In the present paper some behavioral effects of GYKI 52466 were studied in male Wistar rats and male Albino Swiss mice. GYKI 52466 reduced the locomotor activity in normal rats and mice, without evoking any symptoms of behavioral stimulation. The CGP 37849-induced hyperlocomotion was increased by GYKI 52466. The akinesia in monoamine-depleted rats was not affected by the drug studied. The antiakinetic effect of L-DOPA was not changed by GYKI 52466, whereas the antiakinetic effect of L-DOPA+CGP 37849 was decreased. GYKI 52466 increased the hyperlocomotion induced by apomorphine or cocaine. The drug did not change the catalepsy induced by haloperidol or fluphenazine, as well as the anticataleptic effect of CGP 37849. GYKI 52466 was inactive in the forced swimming test, but increased the antidepressant effect of CGP 37849. The flexor and extensor muscle tone of the rats hind limb was not modified by GYKI 52466. The results obtained indicate that GYKI 52466 shows a neuropharmacological profile similar but not identical with that of the quinoxalines (competitive AMPA receptor antagonists) studied previously.

Animals↗