Stereospecific activity of two glutamate analogs.
Two glutamic acid analogs, (+)-(S)- and (-)-(R)-4-(2,2-diphenyl-1,3,2-oxazaborolidin-5-oxo)propionic acid ((+)-(S)- and (-)-(R)-Trujillon, respectively), were prepared. The stereospecific activity of their pharmacological properties was studied. The median convulsant dose (CD(50)) and median lethal dose (LD(50)) were analyzed in female Swiss Webster mice and their effects in vivo on unitary electrical activity in globus pallidus neurons were elucidated in male Wistar rats. Compounds were characterized by (1)H, (13)C, and (11)B nuclear magnetic resonance. The LD(50) of (+)-(S)-Trujillon was 449.08 mg/kg and it increased spontaneous motor activity, while with (-)-(R)-Trujillon there was no mortality up to 1,000 mg/kg and it decreased spontaneous motor activity. The CD(50) in experiments with (+)-(S)-Trujillon was 199.34 mg/kg. Unitary recording in globus pallidus neurons showed i.v. administration (+)-(S)-Trujillon (50 mg/kg) increased frequency 79.0 +/- 23.0% in relation to basal response. (-)-(R)-Trujillon and (+)-(S)-glutamate (50 mg/kg each) did not provoke changes in spontaneous basal firing. Local infusion of (+)-(S)-Trujillon (1 nMol) increased spontaneous firing in most neurons tested by 269.0 +/- 83.0% in relation to basal values. Intrapallidal infusion of (-)-(R)-Trujillon (1 nMol) and saline solution did not cause statistically significant changes in globus pallidus spiking. Results showed that (+)-(S)-Trujillon crosses the blood-brain barrier and has stereospecific activity.
Araujo Alvarez
Juan Manuel
JM
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Departamento de Bioquímica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón, Casco de Santo Tomás, C.P. 11340, México D.F.
Querejeta
Enrique
E
Oviedo
Aldo
A
Trujillo Ferrara
José G
JG
D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D003292:Convulsants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005917:Globus Pallidus / Q000166:cytology / Q000187:drug effects; D005971:Glutamates / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D018698:Glutamic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D051379:Mice; D009474:Neurons / Q000187:drug effects; D013237:Stereoisomerism; D013687:Telencephalon / Q000166:cytology / Q000187:drug effects
D001896:Boron Compounds; D003292:Convulsants; D005971:Glutamates; D007202:Indicators and Reagents; C499262:trujillon; D018698:Glutamic Acid