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Biomedical subjects

G Satzinger

Publications and source records attributed to G Satzinger.

12 recordsLinked to original sources
PubMed2001

Drug discovery and commercial exploitation.

In this report, the author demonstrates the central role of chemistry in pharmaceutical research in the past. Although the modern researcher has a more sophisticated understanding of disease origins and more sophisticated means to new drugs, chemistry and ingenuity remain propelling elements of pharmaceutical research in the twenty-first century. Certainly, long-term experience in commercial drug research suggests that prior to launch, the eventual fate of a drug candidate may be less destined by quality and demand than by discrete decision procedures within top management.

Journal Article↗
PubMed1994

Antiepileptics from gamma-aminobutyric acid.

The importance of GABAergic neurons as the control sites at the central excitation level is generally accepted. Recently, knowledge has expanded concerning the participation of the GABAergic system in the pathophysiology of neurological and psychiatric diseases. Especially the pathogenesis of epilepsy is seen in connection with a loss of neuronal inhibitory function. Investigations into the structure and biochemistry of the central inhibitory transmitter GABA (gamma-aminobutyric acid) and the GABAA receptor resulted in medicinal-chemical strategies to stimulate GABAergic neurotransmission. With the synthesis of the GABA derivatives progabide, vigabatrin and gabapentin, a very promising enrichment of antiepileptic pharmacotherapy has become available.

Animals↗
PubMed1992

Anticonvulsant and sodium channel blocking effects of ralitoline in different screening models.

Ralitoline, a thiazolidinone derivative chemically distinct from known antiepileptic drugs, possesses remarkable anticonvulsant properties as demonstrated in various animal models of epilepsy. The efficacy of this compound seems to be comparable or even better than that of conventional antiepileptics. In the present study, the activity of ralitoline was investigated in four seizure models in rodents in order to characterize the anticonvulsant profile of action further. In the maximal electroshock seizure test (mice), this compound showed marked anticonvulsant effects (ED50 2.8 mg/kg i.p.). The efficacy of clinically established anti-epileptics was significantly increased when ralitoline was given as co-medication. In the strychnine seizure test (mice), ralitoline (5 and 10 mg/kg) prolonged the latency of tonic seizures as well as the survival time. On the other hand, in the subcutaneous pentylenetetrazol seizure threshold test (mice), this drug revealed limited protective actions at higher doses and increased the effectiveness of ethosuximide. In unrestrained rats with chronically implanted electrodes, ralitoline (5 mg/kg) significantly reduced the duration of electrically-evoked hippocampal discharges and raised the focal stimulation threshold (10 mg/kg). In the rotorod ataxia test (mice), a TD50 value of 14.5 mg/kg i.p. was determined for ralitoline (protective index TD50/MES-ED50 5.2). With regard to the possible mode of action, whole-cell voltage-clamp experiments on cultured neonatal rat cardiomyocytes showed that ralitoline may act specifically on voltage-sensitive sodium channels. The compound inhibited the fast sodium inward current in a frequency- and voltage-dependent manner. In conclusion, the findings confirm the potent anticonvulsant effects of ralitoline, especially against generalized tonic-clonic and complex partial seizures. Moreover, in combination with antiepileptics, an additive synergism can be found at lower concentrations. Regarding the mode of action, this drug was capable of depressing the fast sodium inward current in cultured heart ventricular cells, suggesting that the local anesthetic properties may be important for the anticonvulsant activity of ralitoline.

Animals↗
PubMed1991

Ralitoline.

Explore the source record for details and available documents.

Animals↗
PubMed1985

Synthesis, toxicity, and therapeutic efficacy of 4-amino-N-(2'-aminophenyl)-benzamide: a new compound preferentially active in slowly growing tumors.

The present paper describes 4-amino-N-(2'-aminophenyl)benzamide (GOE1734) with regard to synthesis; toxicity in mice, rats, and dogs; and differential therapeutic efficacy in slowly and rapidly proliferating rat tumors. GOE1734, an analog of a group of compounds known for other than antitumor effects with relatively simple N-acyl-O-phenylenediamine structure, is characterized by a low bacterial mutagenic potential after in vitro metabolic activation and DNA-DNA crosslinking activity after in vivo treatment. Maximum tolerated doses in rats and dogs amount to 4 and 1 mg/kg, respectively. High growth-inhibiting efficacy was obtained in intratibially implanted osteosarcoma, in methylnitrosourea-induced primary mammary carcinoma, and in acetoxymethyl-methylnitrosamine-induced colorectal adenocarcinoma. GOE1734 proved to be ineffective in transplanted Yoshida sarcoma and Walker 256 carcinosarcoma when single or multiple doses were administered at dose levels that were moderately toxic or not toxic. Some antitumor effects were observed in L5222 leukemia after ip transplantation, but no effect could be observed after ic implantation or in vitro incubation and subsequent retransplantation of these cells. Since the latter three rat tumors are characterized by relatively short tumor volume doubling times (0.5-2 days), whereas the first three grow slower (tumor volume doubling time, 11-19 days), the remarkable differential antitumor activity of GOE1734 in fast and slowly growing malignancies is striking.

Animals↗
PubMed1977

[2-Carbethoxymethylene-thiazolidones-(4), a novel series of Heterocycles with choleretic properties].

Base-induced condensation of alpha-mercapto-carboxylic esters with activated acetonitriles yields 2-methylene-thiazolidones-(4). The paper presented describes the development of ethyl (Z)-(3-ethyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (30; piprozoline, Gö 919, Probilin), a novel choleretic with exocrin pancreas stimulating and hepatoprotective properties, by following-up the choleretic parent compound 2, which belongs to the 2-carbethoxymethylene-thiazolidones-(4) series. Synthesis and properties of piprozoline are reported. Structure-activity relationship is discussed in short.

Animals↗
PubMed1977

[Structure-activity relationships of etozolin, a novel diuretic (author's transl)].

Selection of a structurally confined group of diuretics out of 2-methylenethiazolidones-(4), a new class of compounds, and related heterocycles with partly choleretic properties is described. The physico-chemical parameters of ethyl (Z)-(3-methyl-4-oxo-5-piperidino-thiazolidin-2-ylidene) acetate (3; etozolin, Gö 687, Elkapin), which has been selected for therapeutic use, are discussed with respect to its close structural relation to the choleretic piprozoline (2). Both the spectroscopic results and the anomalous thermodynamic data of 2, 3 and the homologous compounds 4 and 5 demonstrate a structural specificity of 3 unknown up to now with diuretics.

Chemical Phenomena↗
PubMed1975

[Analytical profile of purified hexetidine (author's transl)].

Physico-chemical, spectroscopic (UV, IR, NMR, mass), chromatographic (GLC, TLC) properties and synthesis of 1,3-bis(2-ethylhexyl)-5-amino-5-methyl-hexahydropyrimidine (hexetidine) are reported and discussed. Moreover, the difference between commercial and purified hexetidine is demonstrated.

Chemical Phenomena↗