[The neurotoxicity of benzodiazepines].
Molecular and clinical effects of benzodiazepines (BDZs) subsequent to their prenatal and postnatal application to animals and man are reviewed. BDZs interactions with neurotransmitter systems and with metabolic processes are presented and analysed. The experimental data obtained after prenatal application indicate that BDZs can cause malformations, functional deficits and long-lasting behavioural anomalies. The prenatal toxicity of BDZs is probably due to their interaction with neurotransmitter systems. Moreover, a BDZs interaction with mechanisms regulating the excitability of cell membranes and protein synthesis could also play a role. The consequences of prenatal exposition to BDZs in man, particularly their behavioural aspects, have not been sufficiently investigated as yet. Postnatal BDZs application can bring about behavioural disturbances and neurological deficits in animals and man. A part of this pathology can be compensated by means of the functional and structural redundance as well as the tolerance. Limitations in functional and morphological reserves of the nervous system can entail severe disturbances, e.g. cardio-respiratory insufficiency. The pharmacological and toxic BDZs effects could partly be due to their interactions with the same molecular mechanisms. These effects can possibly be mediated through BDZs receptors of the central and peripheral type. Regulatory mechanisms for excitability of cell membranes, cellular energetic processes and protein synthesis seem to be particularly sensitive to the BDZs impacts. A close dosis-effect relation for pharmacological and toxic BDZs effects does not seem to exist.
Karkos
J
J
Abt. Experimentelle und Klinische Pharmakologie, Institut für Arzneimittel des Bundesgesundheitsamtes.
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects; D005260:Female; D006801:Humans; D009420:Nervous System / Q000187:drug effects; D009422:Nervous System Diseases / Q000139:chemically induced*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D009435:Synaptic Transmission / Q000187:drug effects
D014151:Anti-Anxiety Agents; D001569:Benzodiazepines
Neurotoxizität von Benzodiazepinen.