ABSTRACT
The toxicity of a series of GABAlytics (11 drugs) representing different pharmacological groups was evaluated in comparative experiments on Daphnia magna Straus and white mice. A high degree of correlation was established between the toxicity of GABA antagonists studied in daphnia and mice. The pharmacological analysis of the interaction of agonists and antagonists of GABA/benzodiazepine/ionophore-receptor complex--the competitive ligands for various binding sites--was carried out. It is suggested that the ability of GABA agonists to prevent the action of GABA antagonists in whole organism is mainly determined by their pharmacokinetic and pharmacodynamic features, rather than by direct competition for binding sites within the receptor complex.
Subject(s)
Daphnia/drug effects , GABA Agonists/toxicity , GABA Antagonists/toxicity , Animals , Ligands , Mice , Mice, Inbred StrainsABSTRACT
Published data and original experimental results are summarized to justify biochemically the use of Daphnia magna Straus as an additional or alternative test object for the study of cholinotropic substances. The data of radioligand analysis provide direct evidence that the organism of Daphnia contains M-cholinoreceptors identical (with respect to pharmacodynamic parameters) to those in the human and animal organism.
Subject(s)
Cholinergic Antagonists/pharmacology , Daphnia/metabolism , Drug Evaluation, Preclinical/methods , Animals , Cats , Dogs , Humans , In Vitro Techniques , Radioligand Assay , Rats , Receptors, Muscarinic/drug effects , Receptors, Muscarinic/metabolism , Species SpecificityABSTRACT
Intermediatory relationships between the cholinergic and dopaminergic neurotransmission systems were analyzed using published data and the original experimental results obtained on Daphnia magna Straus, a new test object. Based on these results, the antihaloperidol activity of a series of M- cholinoblocking agents with different receptor selectivities were studied in comparison to the new cholinoblocker pentifin exceeding in the activity the classical antiparkinsonian drugs such as cyclodol, amedin, and norakin.
Subject(s)
Receptors, Cholinergic/physiology , Receptors, Dopamine/physiology , Animals , Antiparkinson Agents/pharmacology , Cholinergic Antagonists/pharmacology , Daphnia , Receptors, Cholinergic/drug effects , Receptors, Dopamine/drug effects , Synaptic Transmission/drug effectsABSTRACT
Experiments on rodents showed that pentifin, a muscarine antagonist belonging to the group of acetylene amines, possesses a pronounced antiparkinsonian activity. Pentifin is superior in the breadth of therapeutic action and tolerance characteristics to the conventional agents used for Parkinson's disease treatment.
Subject(s)
Acetylene/analogs & derivatives , Acetylene/therapeutic use , Amines/therapeutic use , Antiparkinson Agents/therapeutic use , Muscarinic Antagonists/therapeutic use , Acetylene/adverse effects , Acetylene/pharmacology , Amines/adverse effects , Amines/pharmacology , Amines/toxicity , Animals , Antiparkinson Agents/adverse effects , Antiparkinson Agents/pharmacology , Antiparkinson Agents/toxicity , Catalepsy/chemically induced , Catalepsy/drug therapy , Convulsants , Disease Models, Animal , Dose-Response Relationship, Drug , Drug Antagonism , Drug Evaluation, Preclinical , Haloperidol , Heart Rate/drug effects , Lethal Dose 50 , Memory, Short-Term/drug effects , Mice , Muscarinic Antagonists/adverse effects , Muscarinic Antagonists/pharmacology , Muscarinic Antagonists/toxicity , Pentylenetetrazole , Rats , Seizures/chemically induced , Seizures/drug therapyABSTRACT
Haloperidol and dimethpromide exhibit the properties of dopamine antagonists in the experiments on Daphnia magna Straus (Crustaceae family). Haloperidol, in contrast to dimethpromide, does not significantly influence the toxic effect of apomorphine. It is suggested that acetylene aminoalcohol derivatives are selective ligands for one of the subtypes of dopamine receptors.
Subject(s)
Acetylene/analogs & derivatives , Acetylene/pharmacology , Amino Alcohols/pharmacology , Dopamine/metabolism , Muscarinic Antagonists/pharmacology , Animals , Apomorphine/toxicity , Arecoline/toxicity , Daphnia , Dopamine/toxicity , Dopamine Antagonists/toxicity , Drug Antagonism , Haloperidol/toxicity , Lethal Dose 50 , LigandsABSTRACT
The results of study of the selectivity of the effects of cholinonegative and cholinopositive agents obtained on Daphnia magna hydrobionts were compared with the results of investigations on rats. This allowed Daphnia to be recommended as an alternative test object for studying the selectivity of the effect of cholinotropic agents in relation to some subtypes of muscarine receptors in an intact organism.
