Toxicological and Pharmacological Effects of D‐Arginine

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Abstract
D-Arginine is extensively used in studies on L-arginine/nitric oxide pathway as an inactive form of L-arginine, even in man. In addition, it has previously been reported that this D-amino acid appears to have pharmacological activity. The present work aimed at evaluating the toxicity and pharmacology of D-arginine administered by the intraperitoneally route in albino male mice. Toxicity of D-arginine, alone as well as in the presence of propranolol and betamethasone was evaluated. D-Arginine in mice showed a light toxicity order (DL50: 2800 mg/kg). Previous injection of the beta-adrenoceptor blocker, propranolol (2 mg/kg, intraperitoneally), or betamethasone (0.5 mg/kg, intraperitoneally) produced a decrease in the toxicity of D-arginine (LD50: 3600 mg/kg, 3300 mg/kg, respectively). Also, a neuropharmacological screening of D-arginine using behavioural, neurological, autonomic, barbiturate-induced sleep time and pentylenetetrazole-induced convulsions tests were performed. D-Arginine 700 mg/kg displayed central stimulant properties, whereas a depressant profile was observed at a dose of 1400 mg/kg. In addition, D-arginine 1400 mg/kg produced a potentiation of pentobarbital sleeping time and a marked anticonvulsivant action against pentylenetetrazole.