Flumazenil: a novel and potent benzodiazepine competitive receptor blocker

One of the most rewarding outcomes in the recent research in the field of benzodiazepines [BNZs] is the discovery of BNZ receptors and their association with GABA receptors, together with the discovery of some synthetic BNZ agonists andas antagonists. To the latter group belongs the 1,4-imidazodiazepine derivative-flumazenil which was introduced in 1981. It is shown to be competitive blocker for both types of BNZ receptors, namely, BNZ type-1 which are involved in the anxiolytic effects and BNZ type-2 which are involved in sedation and sleep. Administration of flumazenil [10 micro g/kgi.v] is shown to rapidly antagonize [within minutes] BNZ-induced anxiolytic, sedative,hypnotic, ataxic, anticonvulsant, amnestic and respiratory depressant effects. The major disadvantage of flumazenil is its rapid hepatic metabolism that curtails its oral use. Beside helping in reversal of BNZ- induced intoxication,the drug has been proven to be of value in the diagnosis of unconsciousness of unknown origin, to test for BNZs- involvement and in the improving of consciousness in some cases of hepatic coma. The introduction of flumazenil is expected to give an extended margin of safety to the use of BNZs, but it is hoped that it would not encourage the overwhelming use of these drugs

Effect of the volatile oil of Nigella sativa on the arterial blood pressure and heart rate of the Guinea-Pig

The effects of the volatile oil [V.O.] of the black seed-Nigella sativa Linn, and its constituent thymoquinon [T.Q.] were examined on the arterial blood pressure and the heart rate of urethane-anaesthetized guinea-pigs. Intravenous administration of the V.O. [30-120 micro 1 kg-1] decreased the arterial blood pressure and the heart rate in a dose-depended manner. Similarly, administration of T.Q.[6-24mg kg -1] decreased the arterial blood pressure and the heart rate. Pretreatment of the animals with atropine or cyproheptadine [2 mg kg -1 for 5 min] or with hexamethonium [10 mg kg -1 for 10 min] antagonized V.O. and T.Q.- induced cardiovscular depressant effects. V.O-induced cardiovascular depressant effects were also significantly antagonized by spinal pithing.it was concluded that V.O.-induced effects were probably due to its constituent T.Q. and were probably mediated centrally within the medulla ablongata via activation of 5-hydroxytrptaminergic and muscarinic mechanisms