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At least 217 records · Page 12Linked to original sources

PubMed1991

[Correction of apathetic-abulic manifestations of schizophrenia with cholinotropic drugs].

The authors describe the results of the treatment of 30 patients suffering from schizophrenia with the well-defined apatho-abulic manifestations. The patients received anticholin-esterase agents (galanthamine and deoxypeganin) combined with the M-cholinolytic drug benactyzine. The treatment lasted 3 to 4 weeks. Satisfactory compensation for the deficiency manifestations was attained in 18 patients (60%). The therapeutic dynamics appeared the best in patients with predominant anergic disorders accompanied by well-defined impoverishment of motor functions. The presence of roductive psychotic disorders in the syndromal structure noticeably decreased the treatment efficacy. The deranged capacity for behavioral initiation classified by the authors with the fundamental deficiency manifestations turned out most refractory to the treatment. The polymediator model of the schizophrenic defect is reviewed, according to which the deficiency manifestations represent adaptive stability states with emergence to a lower energy level. In such a case the neuronal populations with different mediator modality become deactivated. On the one hand, this gives rise to a decrease of psychotic productive disorders, on the other one, to the occurrence of the negative manifestations.

Adult↗

PubMed1991

Effectiveness of oral pyridostigmine pretreatment and cholinolytic-oxime therapy against soman intoxication in nonhuman primates.

Nonhuman primates which were fed Mestinon (pyridostigmine) syrup-impregnated food biscuits (40 mg per animal) exhibited a reproducible inhibition of whole blood cholinestrase activity of 40 to 50% for a period of 1 to 6 hr. Pyridostigmine pretreatment was supplemented by therapy with two doses of an antidotal combination (A,TM,B) consisting of 0.05 mg/kg atropine, 2.24 mg/kg TMB-4, and 0.4 mg/kg benactyzine which assured survival in five of six animals following three separate exposures to 10 LD50 soman. The protective period of this oral dose of pyridostigmine supported by A,TM,B therapy was between 1/2 and 8 hr. Oral pyridostigmine pretreatment in combination with atropine therapy (three doses of 0.07 or 1.00 mg/kg im) also saved monkeys exposed to 10 LD50 soman; however, the period of recovery was prolonged. Oral pyridostigmine pretreatment did not alter the lethality of soman in the absence of A,TM,B or atropine therapy.

Administration, Oral↗

PubMedDate not supplied

[Effect of autonomotropic agents and their combinations with amidopyrine on aesptic inflammation and vascular permeability].

Experiments staged on rats demonstrated the display of antiexudative activity by phepracet, deseryl, chlorpromazine, phentolamine and sanotension in an inflammation produced through subplantar introduction of the Difco agar. Some of the above agents suppressed the reaction in response to dimethyl sulfoxide injection. The antiedematous and stabilizing the cellular membranes effects of amidopyrine were potentiated by using the latter in combination with sympatholytics and also with benactyzine. No synergism with respect to changes of the vascular permeability and kinnase activity of the blood was revealed.

Acetamides↗

PubMedDate not supplied

[Effect of tranquilizers on impulse conduction in the afferent pathways of visceral nerves].

Experiments on pyrolaxon-immobilized cats evidence that diazepam produces depression of evoked potentials in the specific, nonspecific and associative brain structures upon an electric stimulation of the visceral and somatic nerves, and also with accoustic and photostimulation; Meprotan (meprobamate) in doses of 40-100 mg/kg neither changes nor increases, and in doses of 100-150 mg/kg, reduces the amplitude of evoked potentials and at the sme time forces down the arterial pressure. Amizyl (benactyzine) inhibits the potentials evoked by stimulation of the vagus. The amplitude of responses arising on stimulation of the inferior cardiac, celiac and sciatic nerves, and also with acoustic and photostimulation neither changes nor increases.

Animals↗

PubMed1987

Nonmuscarinic neurotoxicity of oxotremorine.

The ability of various treatments to prevent peripheral parasympathetic actions, central effects and lethality of the muscarinic agonist oxotremorine was studied in rats. The percentage of animals exhibiting effects of oxotremorine was dose and time dependent. The ED50 for producing lacrimation, salivation, tremor, convulsions and death was 2.5, 1.3, 1.6, 3.2 and 8.3 mg/kg i.p., respectively. Pretreatment with 5 mg/kg of atropine completely prevented all observable effects of oxotremorine at doses of 5 mg/kg and below. Doses of oxotremorine in excess of 5 mg/kg produced tremor, generalized clonic convulsions and death that could not be prevented by atropine when given at up to 160 mg/kg; lacrimation and salivation were not present in atropine-treated rats. In the presence of 40 mg/kg of atropine, ED50 values for oxotremorine were shifted more than 12-fold for lacrimation, salivation and tremor, whereas convulsions and death were maximally altered by a factor of 2. Scopolamine, benactyzine and benztropine were also incapable of completely preventing tremor, convulsions and death induced by 10 or 15 mg/kg of oxotremorine. Atropine methyl nitrate had effects comparable to atropine sulfate on lacrimation, salivation and lethality induced by oxotremorine (10 or 15 mg/kg) but had no effect on tremor or convulsions. A similar profile of atropine-insensitive effects was produced by pilocarpine and arecoline. Doses of diazepam 4 times higher (4 mg/kg) than necessary to prevent tonic-clonic convulsions induced by pentylenetetrazol were ineffective against tremor, convulsions or death produced by oxotremorine (10 or 15 mg/kg) unless given in conjunction with atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

[Effect of m-cholinoblockaders and physostigmine on emotional reactivity and catecholamine metabolism in the brain of rats].

In experiments on male albino rats m-choline blocking agents, atropine and benactyzine potentiated the stimulating effect of l-DOPA on emotional reactivity and aggressiveness, while physostigmine antagonized behavioral effects of l-DOPA. Both the choline blocking agents and physostigmine lowered the brain dopamine accumulation rate after introduction of l-DOPA, at the same time raising the level of homovanilic acid dopamine metabolite. It is suggested that the effect of cholinergic compounds on emotional reactivity and aggressiveness of the animals depends in part on the activity of the brain dopaminergic system.

Aggression↗

PubMedDate not supplied

[Effect of M-and N-cholinolytics on the content of Ca2+ in synaptosomes and metabolism of phosphoinositols in the rat brain].

M-cholinolytics benactyzine and glypine increased a permeability of neurone membranes for Ca2+, producing the ion accumulation in synaptosomes. N-cholinolytic thropacin did not exhibit this effect and diphacyl caused similar to the M-cholinolytics but only slight effect on the Ca2+ content. The M-cholinolytics increased phosphoinositol turnover in rat brain, while the N-cholinolytics decreased its metabolism. These data obtained suggest that the M-cholinolytics interact selectively with phosphoinositols of neurone membranes affecting the affinity of phosphoinositols to two-valent cations and elevating the ability of Ca2+ to penetrate across neuronal membranes.

Animals↗

PubMed1983

Soman-induced depression of brain activity in TAB-pretreated rats: 2-deoxyglucose study.

Administration of large doses of Soman (2xLD50) to rats protected with TAB, a mixture of trimedoxime (TMB-4), atropine and benactyzine, results in approximately 2-fold reductions of local cerebral glucose utilization (LCGU) in most brain regions. This is in contrast to the marked increase in LCGU that is observed in conjunction with the seizures associated with an LD50 dose of Soman given to unprotected rats. This study reveals that TAB is effective in protecting against Soman-induced seizures, but only at the expense of a severe decrease in LCGU after Soman exposure.

Animals↗

PubMed1978

[Effect of pharmacologic substances on the dominance-submission relationship in a pair of rats].

The effect of neuroleptics (chlorpromazine, trifluoperazine, haloperidol), antidepressants (amitryptyline, imipramine), tranquilizers (diazepam, chlordiazepoxide, benactyzine) and stimulant d-amphetamine on the domination and subordination relations formed as a result of competitive behaviour in a pair of rats was studied. The drugs in question proved to violate the set relations of domination and subordination weakening the attacking ability of dominating rats and strengthening the defensability of the subordinate ones. With increase of antidepressants dosage received by a subordinate rat its competing ability becomes enhanced too; this may cause a change in domination.

Amitriptyline↗

PubMedDate not supplied

[Role of disorders in biogenic amine metabolism in the pathogenesis of botulin poisoning].

A depotentiating effect of prednisolone, benactyzine, reserpine, propranolole and large doses of serotonin on the development of the intoxication was shown to occur in combination with inhibition of the biogenic amines accumulation in various tissues of cats with botulinic paresis. The same phenomenon was observed in intoxicated animals maintained without pharmacological treatment.

Animals↗

PubMedDate not supplied

Protection and inflammatory markers following exposure of guinea pigs to sarin vapour: comparative efficacy of three oximes.

The purpose of the present study was to compare the antidotal efficacy and the combined effects on inflammatory markers of three oximes--toxogonine, TMB4 and 2-PAM--in combination with anticholinergic drugs following exposure to sarin vapour by inhalation. Guinea pigs restrained in plethysmographs were exposed to various doses of sarin vapour (in the range of 1.4-4.4LD50). The antidotal mixture was injected immediately (5-20 s) following exposure (3 mg kg(-1) atropine and 1 mg kg(-1) benactyzine in combination with 6 mg kg(-1) toxogonine, 2 mg kg(-1) TMB4 or 12 mg kg(-1) 2-PAM). Bronchoalveolar lavage (BAL) samples were taken from surviving animals 24 h after exposure to determine the levels of inflammatory markers. A differential cell count was performed in BAL samples on Giemsa-stained slides. The inflammatory markers--histamine and prostaglandins (PGE)--were measured in BAL using radioimmunoassay (RIA) techniques. The survival rate in the various treatment groups and analysis of BAL samples showed that: (i) Toxogonine, TMB4 and 2-PAM, without pyridostigmine pretreatment, at doses that were proportional to their doses in the respective auto-injectors, exhibited similar antidotal efficacy against sarin exposure. (ii) The results demonstrated that a centrally acting anticholinergic drug is essential in the antidotal mixture to ensure survival. (iii) Histamine release and eosinophilia following sarin inhalation might require additional intervention, aimed at reducing the symptoms of allergic reaction and possibly expediting recovery.

Animals↗

PubMed1998

Prophylaxis against soman inhalation toxicity in guinea pigs by pretreatment alone with human serum butyrylcholinesterase.

Human butyrylcholinesterase (HuBChE) has previously been shown to protect mice, rats, and monkeys against multiple lethal toxic doses of organophosphorus (OP) anticholinesterases that were challenged by i.v. bolus injections. This study examines the concept of using a cholinesterase scavenger as a prophylactic measure against inhalation toxicity, which is the more realistic simulation of exposure to volatile OPs. HuBChE-treated awake guinea pigs were exposed to controlled concentration of soman vapors ranging from 417 to 430 micrograms/liter, for 45 to 70 s. The correlation between the inhibition of circulating HuBChE and the dose of soman administered by sequential i.v. injections and by respiratory exposure indicated that the fraction of the inhaled dose of soman that reached the blood was 0.29. HuBChE to soman molar ratio of 0.11 was sufficient to prevent the manifestation of toxic signs in guinea pigs following exposure to 2.17x the inhaled LD50 dose of soman (ILD50, 101 micrograms/kg). A slight increase in HuBChE:soman ratio (0.15) produced sign-free animals after two sequential respiratory exposures with a cumulative dose of 4.5x ILD50. Protection was exceptionally high and far superior to the currently used traditional approach that consisted of pretreatment with pyridostigmine and postexposure combined administration of atropine, benactyzine, and an oxime reactivator. Quantitative analysis of the results suggests that in vivo sequestration of soman, and presumably other OPs, by exogenously administered HuBChE, is independent of the species used or the route of challenge entry. This assuring conclusion significantly expands the database of the bioscavenger strategy that now offers a dependable extrapolation from animals to human.

Animals↗

PubMed1993

Biphasic action of sarin on monosynaptic reflex in the neonatal rat spinal cord in vitro.

The action of sarin, an organophosphorus (OP) compound, was examined in vitro for its effects on the spinal monosynaptic reflex (MSR) in neonatal rats. The effects of sarin were biphasic, i.e. facilitation at lower concentrations (2-20 nM) followed by depression of the MSR at concentrations above 30 nM. Facilitation of MSR was maximal (150% of control) at 20 nM sarin. The depression of MSR was maximal (70% of control) at 200 nM sarin, with half maximal inhibition occurring at 90 nM sarin. Atropine (200-500 nM) effectively reversed the depression caused by sarin, while pretreatment with low concentrations of atropine (10 nM) completely blocked the depression otherwise observed with sarin. Benactyzine was also effective in preventing sarin-induced depression, while pirenzepine was less effective. The nicotinic blocking agents tubocurarine and mecamylamine were, however, ineffective in preventing or reversing sarin-induced depression. The facilitation of MSR seen with lower concentrations (2-20 nM) correlated well with the blockade of late phase inhibition (between 30 and 50 ms conditioning-test interval) elicited in spinal cord by stimulating the adjacent dorsal root at various condition-test intervals, which has been shown elsewhere to be sensitive to bicuculline (Deshpande and Warnick 1988). Thus it is speculated that sarin at lower concentrations blocks GABA transmission, producing facilitation, and at higher concentrations activates the muscarinic receptors producing depression of MSR. The beneficial action of pretreatment with antimuscarinic agents may be attributed to the protection of the muscarinic receptors.

Animals↗

PubMed1994

Sensitive and rapid behavioral differentiation of N-methyl-D-aspartate receptor antagonists.

Behavioral effects of PCP-type noncompetitive antagonists of N-methyl-D-aspartate (NMDA) receptors overlap with those of a host of other centrally acting compounds. In the present experiment, locomotor activity and performance on an inverted screen test in untrained mice were used to differentiate PCP-type non-competitive NMDA antagonists from other drug classes. These uncompetitive NMDA antagonists [PCP, dizocilpine, (-)-MK-801, TCP, (+)-SKF 10,047, dextrorphan, ketamine] produced dose-related increases in locomotor activity and the percentage of mice falling off an inverted, elevated wire mesh screen. Both effects demonstrated stereoselectivity, occurred at comparable dose levels, and were within the range of doses producing other biological effects (e.g., anticonvulsant). The potencies of these drugs for producing behavioral effects were positively correlated with affinities for PCP ([3H]MK-801) but not sigma([3H]SKF 10,047) receptors. Although muscarinic antagonists (benactyzine, atropine) produced effects in the same direction, locomotor stimulation was small and occurred at lower doses than those inducing screen failures. Competitive NMDA antagonists (LY 274614, LY 233536, CPP, NPC 12626), sigma receptor ligands (DTG, dextromethorphan), postsynaptic dopamine agonists (quinpirole, SKF 38393) and antagonists (haloperidol, SCH 39166), and some depressant compounds (morphine, diazepam) increased failures on the screen test but decreased locomotor activity. Ligands of the polyamine regulatory site of the NMDA receptor (ifenprodil, SL 82.0715-10) and the AMPA receptor antagonist NBQX decreased locomotor activity without increasing screen failures. An antagonist of the strychnine-insensitive glycine receptor (7-chlorokynurenic acid) did not affect performance on either test. Psychomotor stimulants (cocaine and methamphetamine) stimulated locomotor activity without affecting screen performance. The only false positives occurred with barbiturates (pentobarbital, phenobarbital). Nonetheless, the present procedure demonstrates excellent sensitivity and power for rapid discrimination of uncompetitive NMDA antagonists.

2-Amino-5-phosphonovalerate↗

PubMed1979

Effects of antidepressants and anticholinergics in a mouse "behavioral despair" test.

A new "behavioral despair" test previously asserted to be selectively sensitive to antidepressant treatments was examined for specificity. The results of the present study demonstrate that, in addition to antidepressants, agents with anticholinergic properties such as scopolamine, danitracin, benactyzine, benztropin, clozapine and cyproheptadine also reduce immobility in this test. These results indicate that the swim test in mice cannot be considered selectively sensitive to antidepressants.

Animals↗

PubMed1983

Structure-activity requirements for hypotension and alpha-adrenergic receptor blockade by analogues of atropine.

The hypotensive action of various antimuscarinic compounds structurally related to atropine was studied in conscious, unanesthetized rats. The alpha-adrenolytic activity of these agents was assessed both in vivo (blockade of norepinephrine-induced pressor response) and in vitro (displacement of [3H]WB-4101 binding). Benztropine, homatropine and hyoscyamine caused hypotension and produced alpha-adrenergic receptor blockade similar to atropine. Other analogues were either inactive (atroscine, scopolamine, tropic acid and tropine) or evoked nonspecific changes in blood pressure and lacked alpha-adrenolytic activity (benactyzine, eucatropine, methylatropine, methylhomatropine and methylscopolamine). Based on these data, we propose the following structure-activity relationship for hypotension and alpha-adrenolytic activity: (a) the tropine moiety is inactive unless it is attached to another group by an ester linkage, (b) chemical modification of the tropine moiety, including quaternization, decreases potency, (c) the d-stereoisomer appears to be more potent than the corresponding 1-form.

Acetylcholine↗

PubMed1977

Discriminable effects of antimuscarinics: dose response and substitution test studies.

In a shock escape T-maze task, rats were trained to turn right following one drug treatment and left following a second drug treatment. The specific drug and dose conditions were the only discriminative cues available to the animals. The number of training sessions before criterion performance indicated the discriminability of the two training conditions. Drug vs no drug training showed that discriminability was proportional to dosage for low doses, but was constant over a range of higher doses. Such an asymptote of discriminability was observed with scopolamine, atropine, benactyzine and Ditran (JB 329), and was shown not to result from tolerance. High dose vs low dose discriminations involving scopolamine were learned very slowly if both doses were within the asymptotic range; this indicates that similar discriminable effects were produced by high and low doses. To compare various drugs, substitution tests were administered to trained rats. The four antimuscarinic drugs generally substituted for one another but did not mimic and were not mimicked by drugs in other pharmacological classes. Some exceptions to this pattern were noted. The discriminable effects of scopolamine were partially antagonized by physostigmine. The results indicate that the antimuscarinic drugs share discriminable actions probably produced by their anticholinergic actions. The asymptote of action at high doses appears genuine, possibly reflecting receptor saturation.

Animals↗

PubMedDate not supplied

A study of the N-methyl-D-aspartate antagonistic properties of anticholinergic drugs.

Drugs that act at the N-methyl-D-aspartate (NMDA) receptor complex have the ability to terminate nerve agent-induced seizures and modulate the neuropathologic consequences of agent exposure. Drugs with mixed anticholinergic and anti-NMDA properties potentially provide an ideal class of compounds for development as anticonvulsant treatments for nerve agent casualties. The present experiment evaluated the potential NMDA antagonist activity of 11 anticholinergic drugs by determining whether pretreatment with the compound was capable of protecting mice from the lethal effects of NMDA. The following anticholinergic drugs antagonized NMDA lethality and are ranked according to their potency: mecamylamine > procyclidine = benactyzine > biperiden > trihexyphenidyl. The anticholinergics atropine, aprophen, azaprophen, benztropine, 3-quinuclidinyl benzilate (QNB), and scopolamine failed to show NMDA antagonist properties. In addition, and unexpectedly, diazepam, ethanol, and pentobarbital were also shown to be capable of antagonizing NMDA lethality over a certain range of doses. The advantages and limitations of using antagonism of NMDA lethality in mice as a bioassay for determining the NMDA antagonist properties of drugs are also discussed.

Animals↗