Significance of various adrenoreceptors for brain resistance to total ischemia

Kulinskii, V. I.; Medvedeva, T. N.

doi:10.1007/bf02446619

Cited by 4 publications

(8 citation statements)

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“…Proxodolol and labetalol exhibited no protective action with respect to the cerebral ischemia, while propranolol, prazosin, and especially clophelin produced a neuroprotective effect manifested by a considerable prolongation of the survival life of mice (see Table 1), in agreement with the published data for clophelin [6]. The neuroprotective action of clophelin was not significantly affected by proxodolol and labetalol, whereas the effects of prazosin and clophelin were added and propranolol even potentiated the action of clophelin (by a factor of2.4,p < 0.001).…”

supporting

confidence: 90%

Effect of proxodolol and other adrenoblocking agents on the pharmacological properties of clophelin

Mashkovskii¹,

Kulinskii²,

Паршин³

et al. 1997

Pharm Chem J

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Proxodolol is a new Russian [3,ct-adrenoblocking drug possessing antihypertensive, antiischemic, and antiglaucomatosis properties [1 -4]. This drug is already used in practical ophthalmology for reducing the intraocular pressure in patients diagnosed with glaucoma.The complex chemotherapy of glaucoma involves, in addition to [3-adrenoblocking agents and pilocarpin, the administration of elophelin (clonidine). Because this drug has a high criminogenic potential, it was of interest to study the effect of proxodolol and some other adrenoblocking agents on the main pharmacological manifestations of clophelin. METHODSa) Effect of drugs on the body temperature and the course of cerebral ischemia. Experiments were performed on a group of 209mice (CBA. C57B1)F1 weighing 19-27 g. The body temperature of mice was measured at a depth of 3.5 cm with a TPEM-1 electric thermometer. The drug effects were studied on a decapitation model of total cerebral ischemia and involved determination of the duration of agonal breathing. Clophelin was introduced 30 min before decapitation at a dose of 1 mg/ kg (s.c.), and adrenoblocking drugs were injected 45 rain before decapitation: proxodolol and labetalol (30 mg/kg, s.c.), propranolol (10 mg/kg, s.c.), b) Sedative effect. Experiments were performed on a group of 144male mongrel mice weighing 18-20 g. The spontaneous motor activity was determined using an OptoVarimex instrument (Italy) every 10 rain during a time period of 60 min. Clophelin at a dose of (0.5 mg/kg, i.p.) and proxodolol (2 mg/kg, i.p.) were introduced either separately or in combination (a new ophthalmic medication form); timolol at a dose of 2 mg/kg (i.p.) was also injected either either separately or in a combination with clophelin (0.5 mg/kg, i.p.). c) Effect on the coordination of movements. Experiments were performed on 30 male mice weighing 18-20 g divided into groups of 5 animals. The manifestations of motor disorder were evaluated using the "rotating rod" test. Each group was placed on the testing device (Ugo-Basile, Italy), and the number of mice incapable of staying on the rotating rod was counted. The animals were injected intraperitoneally with solvent (0.1 ml of 0.9 % sodium chloride), proxodolol (2 mg / kg), clophelin (0.5 or 1 mg / kg), or a combination of the two drugs (a new ophthalmic medication form) at a dose of 0.5 or I mg/kg, as calculated for clophelin. d) Hypotensive action. Experiments were performed on a group of 4 rabbits weighing 2.5 -4 kg narcotized with urethane (1.2 g/kg, i.v.). The arterial pressure in a common carotid artery was measured with a mercury manometer and recorded on a smoked tape of kymograph. Clophelin was in-0091 -150X/97/3104--0163518.00 9 1997 Plenum PuNishing Corporation

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supporting

confidence: 90%

Effect of proxodolol and other adrenoblocking agents on the pharmacological properties of clophelin

Mashkovskii¹,

Kulinskii²,

Паршин³

et al. 1997

Pharm Chem J

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“…Not only pro-0007-4888/97/0010-0984518. The high NPE of methyldopa, guanabenz, and clonidine [1] is supported by extensive experimental data. Combined administration with epinephrine resulted in a clear-cut NPE, but for propranolol and prazosin it was significantly higher than for the antagonist itself.…”

Section: Resultsmentioning

confidence: 70%

“…

Epinephrine does not change the resistance of brain to total cerebral ischemia (CI), although its effect is manifested against the background of propranolol [1]. Shnilar effects of other adrenoceptor antagonists were not studied, c~2-Agonists produce a marked neuroprotective effect (NPE), i.e., the cerebral protective effect, which was demonstrated in various models of CI [1,2,[6][7][8]. It is generally accepted that to prove the role of cm~ain receptors in any physiological effect means to use blockade analysis.

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mentioning

confidence: 99%

“…Epinephrine does not change the resistance of brain to total cerebral ischemia (CI), although its effect is manifested against the background of propranolol [1]. Shnilar effects of other adrenoceptor antagonists were not studied, c~2-Agonists produce a marked neuroprotective effect (NPE), i.e., the cerebral protective effect, which was demonstrated in various models of CI [1,2,[6][7][8].…”

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confidence: 99%

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Role of α2-adrenoceptors in brain resistance to total ischemiaadrenoceptors in brain resistance to total ischemia

Kulinskii

Medvedeva

1997

Bull Exp Biol Med

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Neuroprotective effect of epinephrine is revealed against the background of pmzosin, 13antagonists and their combinations protect against cerebral ischemia, c~2-Antagonists (but not 0~) block the neuroprotective effect of these combinations, methyldopa, guanabenz, clonidine, and oxymetazoline and decrease brain resistance to ischemia, a2-Adrenocept015 participate in the endogenic mechanism of brain resistance to ischemia and in the neuroprotective effect.Epinephrine does not change the resistance of brain to total cerebral ischemia (CI), although its effect is manifested against the background of propranolol [1]. Shnilar effects of other adrenoceptor antagonists were not studied, c~2-Agonists produce a marked neuroprotective effect (NPE), i.e., the cerebral protective effect, which was demonstrated in various models of CI [1,2,[6][7][8]. It is generally accepted that to prove the role of cm~ain receptors in any physiological effect means to use blockade analysis. NPE of clonidine [1] and dexmedetomidine [6] is blocked by ~2antagonists. The respective data are still absent for agonists of dihydroxyphenylethanolamine and aminoguanidine groups. Moreover, idazoxan, an efficient blocker of (z2-receptors , protects the brain against CI [5,8]. The aim of the present study was to elucidate the role of 0~2-adrenoceptors in resistance to total CI with the help of the blockade analysis.

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“…The coincidence of results obtained by twoby two independent methods (comparison of effects of selective receptor agonists and blockade with selective antagonists) indicates that NPE is mediated via GABA receptors of both types. It differs strikingly from NPE of catecholamines and their derivatives, which is mediated only via %-adrenoceptors [1]. However, the most important GABA effect, namely, the decrease in functional cerebral activity, is also realized via GABA receptors of both types [5,6, I 1 ].…”

Section: Resultsmentioning

confidence: 99%

Effect of bilateral destruction of the subretrofacial area on receptor mechanisms of neuroprotective effect of GABAergic agents

Kulinskii

Mickhel'son

1998

Bull Exp Biol Med

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Both GBA A (muscimol, gaboxadol, and isonipecotate) and GABA B (baclofen) receptor agonists produce marked neuroprotective effect during total brain ischemia. The antagonists of GABA^ receptors bicuculline and picrotoxin attenuate the effect of muscimol, and the GABA a receptor antagonists hydroxysaclofen and aminovaleriate decrease the effect of baclofen. The GABAergic substances protect the brain via GABA receptors of both types. The effect of the GABA agonists is central in nature. Key Words: GABA receptors; neuroprotectors; brain ischemia,/-Aminobutyric acid (GABA) is the main inhibiting transmitter in the brain. Its effect is realized via different signal-transducing systems: 1) ionotropic GABA A receptors, which are C1--channels that hyperpolarize cells due to inflow of chloride ions; and 2) metabotropic GABA B receptors, which open K § and close Ca 2 § channels via Gi/~ proteins and inhibit adenylyl cyclase [5,6,13]. Recently, GABA B receptors were cloned [8]. The agonist of GABA s receptors baclofen has a pronounced neuroprotective effect (NPE) during brain ischemia in the rodents [2,3,7,9]. The data on muscimol, an agonist of GABA A receptors, are equivocal [7,10,12]. The effects of GABA receptor antagonists were studied only for NPE of baclofen [7].Our aim was to elucidate the receptor mechanisms of NPE of GABA-ergie agents using two independent methods: 1) comparison of activity of selective agonists of different GABA receptors and 2) blockade of the effects by selective antagonists [5,6,13]. MATERIALS AND METHODSThe study was carried out on 372 CBA and C57B1 mice of both sexes weighing 18-25 g. The following

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Significance of various adrenoreceptors for brain resistance to total ischemia

Abstract: Note. Significance of differences: lp<0.01, 2p<0.001 (compared with the control); 3p<0.01, 4p<0.001 (compared with the antagonist); Sp<0.05, ~p<0.01, 7p<0.001 (compared with clonidine).

Cited by 4 publications

References 4 publications

Effect of proxodolol and other adrenoblocking agents on the pharmacological properties of clophelin

Effect of proxodolol and other adrenoblocking agents on the pharmacological properties of clophelin

Role of α2-adrenoceptors in brain resistance to total ischemiaadrenoceptors in brain resistance to total ischemia

Effect of bilateral destruction of the subretrofacial area on receptor mechanisms of neuroprotective effect of GABAergic agents

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