Toxicological and pharmacological effects of D-arginine.
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.
Navarro
Eduardo
E
Department of Pharmacology, Faculty of Medicine, University of La Laguna, Tenerife, Spain. enavarro@ull.es
Alonso
Simeona J
SJ
Martín
Felipe A
FA
Castellano
Miguel A
MA
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity*; D001341:Autonomic Nervous System / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects*; D001623:Betamethasone / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006993:Hypnotics and Sedatives; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010433:Pentylenetetrazole; D010634:Phenobarbital; D011433:Propranolol / Q000494:pharmacology; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012890:Sleep / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D006993:Hypnotics and Sedatives; D001120:Arginine; D001623:Betamethasone; D011433:Propranolol; D010433:Pentylenetetrazole; D010634:Phenobarbital