N. I. Andreeva

Synthesis and study the pharmacological activity of derivatives of 5-dimethylaminopyrano[3,2-c]quinolin-2-ones

A simple method of synthesizing derivatives of 5-dimethylaminopyrano[3,2-c]quinolin-2-ones is proposed which involves obttaining 4-chloro- or 4-oxo-3-formylquinolines using compounds having an active methylene group. The pharmacological activity of the synthesized compounds is studied.

New potential antihypoxants based on 2-ethyl-3-(N,N-dimethylcarbamoyloxy)-6-methylpyridine

It is established that succinic acid is capable of potentiating (synergism) the antihypoxic activity of 3-hydroxypyridine derivatives such as the succinate (Ia) and hydrochloride (Ib) of 3-(N,N-dimethylcarbamoyloxy)- 2-ethyl-6-methylpyridine. This effect makes it expedient to create new drugs containing a mixture of Ia or Ib and succinic acid derivatives that would possess antihypoxic, antiamnestic, and anticonvulsant activity. The antihypoxic activity of 3-hydroxypyridine drugs increases in the order emoxypin < mexidol < proxypin < Ia + succinic acid < Ib + succinic acid.

Synthesis and psychotropic activity of 3-oxo-1,2,3,5-tetrahydropyrido[1,2-a]-benzimidazole-4-carboxylic acid arylamides

As is known, the GABA-A receptors are capable of interacting with various compounds containing heterobicyclic and/or heterotricyclic fragments and possessing high affinity for the so-called benzodiazepine binding sites. The main classes of these compounds are derivatives of benzodiazepine, 13-carboline, imidazopyridine, pyrazoloquinoline, and imidazoquinoxaline, among which there are substances exhibiting anticonvulsive, sedative, and anxiolytic activity [l]. As was recently established, 3-oxo-l,2,3,5-tetrahydropyrido[1,2-a]benzimidazole-4-carboxylic acid amides (I) are also capable of interacting with GABA receptors at the benzodiazepine binding sites [1]. This fact suggests that the group of amides I may contain compounds possessing psychotropic properties. In order to verify this hypothesis, we have synthesized a new group of amides ( I a Ig) on the basis of a principal scheme of synthesis suggested (without experimental details) previously [1]. A key compound in this scheme is the ethyl ester of 3-oxo-l,2,3,5-tetrahydropyrido[l,2-a]benzimidazole-4-carboxylic acid (II) obtamined proceeding from an ester of [ l-(2-cyanoethyl)benzimidazol-2-yl]acetic acid (III) as describred in the patent [2].

Synthesis and pharmacological activity of new incazan analogs

As a continuation of our studies [3] on the relationship between the biological activit~ structural factors, and the nature of substituents in pyrazino [l,2,3-l,m]-~-carboiine which is the base of the antidepressant incazan [i], we synthesized and studied the pharmacological activity of the following new analogs of that compound: 4-benzyl (I) and 4-cyciohexyl(iI) 10-methoxy-4H-l, 2,5,6-tetrahydropyrazino [1,2,3-1, m]-~-carboiines, 4-desmethyiincazan (IiIa), the 3-methyl isomer of incazan (IIIb) as well as the 10-cyclohexyi derivatives (IIIc) and (IV).

A potential combined formulation containing vinpocetin and succinic acid

Succinic acid bas been found to be able to potentiate the antihypoxic activity of vinpocetin. This property (potentiation) provided grounds for creating a new combined formulation containing vinpocetin and succinic acid, which has more marked antihypoxic activity than the initial single-substance vinpocetin formulation, along with antiamnestic and anticonvulsive activities.

Combined Action of the Anticholinesterase Drug Aminostigmine and the Antidepressant Pyrazidole on Mnemonic Function in Rats and Mice

The effect of aminostigmine alone and in combination with pyrazidole on mnemonic function in rats and mice was studied using passive avoidance conditioned reflex. Aminostigmine is comparable with the reference drug galanthamine in the ability to improve learning and memory, while the aminostigmine - pyrazidole combination even exceeds the reference drug in this respect. Pyrazidole also potentiates the antiamnesic effect of galanthamine. A combination of pyrazidole (possessing no anticholinesterase properties) with anticholinesterase agents can be useful for the complex treatment of dementia.

Synthesis and Pharmacological Activity of N-Arylamidine Derivatives

A series of eleven N-arylamidine derivatives were synthesized and tested for anti-inflammatory, analgesic, and antipyretic properties. In these respects, the synthesized compounds exhibit no advantages over the reference drugs ibuprofen and paracetamol.

Pharmacological properties of digam—A new potential nootropic drug

In recent years, neural-mental diseases have been widely treated with the aid of nootropic drugs whose action consists, to a considerable degree, in affecting the GABA-ergic processes in brain. The parent compound (GABA) in the form of drugs such as gammalon and aminalon is used for treating mental retardation in children, senile dementia in adults, memory and speech disorders upon injury or traumatic brain damage, alcoholic encephalopathy, and so on. However, both GABA and other mediating amino acids (glutamic, aspartic, etc.) poorly penetrate through lipid membranes, including the blood-brain barrier. This probably accounts for the necessity of GABA administration at large doses (up to 3 4 g per day). In this connection, an important current task is the search for compounds structurally analogous to GABA, capable of more readily penetrating through the blood-brain barrier to produce a more pronounced therapeutic effect. For solving this task, specialists of the Chemical Drugs Center have synthesized a series of compounds containing the main fragment of the GABA molecule linked to a lipophilic base. The pharmacological and neurochemical investigations showed that some of these derivatives possess a psychotropic (primarily, nootropic) activity, exceeding in this respect the initial molecule (GABA). The most active compound was named digam. The purpose of this work was to study the acute toxicity and characterize the psychotropic activity of digam with respect to nootropic, antidepressant, sedative (calming), and anxiolytic action.

Antidepressant-enhanced analgesic action of clonidine

Previously we have found that antidepressants such as imipramine, pyrazidol, incazan, and nialamide possess hypoalgesic activity and are capable of enhancing the action of anal~n and promedol [i]. It was also established that pyrazidol, incazan, and imipramine decreases the effect of small doses of clonidine (including the hypotensive and hypolocomotor action and the EEG synchronization reaction) and increase that effect of large doses (manifested by aggressive behavior and the EEG desynchronization reaction) [2, 3]. The influence of these antidepressants on the analgesic properties of clonidine were not characterized. It was reported that tricyclic antidepressants of the type of amitryptiline may increase the analgesic action of clonidine [4]. Therefore it was of interest to study modification of the analgesic effect of clonidine under the action of original russian antidepressant drugs-reversible inhibitors of monoamine oxidaze A (MAO-A), including pyrazidol, tetrindol, and incazan, the tricyclic antidepressant azaphen, the for-

Pyrazinocarbazoles: A new class of tetracyclic pharmacologically active compounds. Part I. Psychotropic activity of pyrazinocarbazole derivatives

One possible way to create new psychotropic drugs consists in modification of the base structure of the known compositions, in particular, by converting them from tricyclic to tetracyclic compounds [I]. This approach was implemented at the Center for Drug Chemistry (Moscow) for the synthesis of original pyrazinocarbazole derivatives. We proceeded from tricyclic compounds ! and connected their aminoalkyl fragment so as to obtain an isosteric tetracyclic pyrazinocarbazole structure 1I [2 6]: