RESUMO
A series of 3-substituted 1-(aminomethyl)-3,4-dihydro-5-hydroxy-1H-2- benzopyrans were prepared as potential D1 selective antagonists. The compounds were evaluated for their affinity and selectivity for the D1 receptor as well as for their functional antagonism of D1-mediated pharmacological events. The compounds show potent D1 antagonist properties in vitro. The optimum nitrogen substitution was found to be the primary amine and the observed order of potency for substitution at the 6-position is OH greater than Br greater than H greater than OMe. Two representative compounds, the 6-methyl and 6-bromo analogues, were also evaluated in vivo for dopaminergic activity. Interestingly, both compounds behave as potent in vivo agonists.
Assuntos
Cromanos/farmacologia , Antagonistas de Dopamina , Inibidores de Adenilil Ciclases , Cromanos/síntese química , Cromanos/metabolismo , Dopamina/farmacologia , Estrutura Molecular , Receptores Dopaminérgicos/metabolismo , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Relação Estrutura-AtividadeRESUMO
This paper describes the rationale for inclusion on community and public health principles and concepts in the optometric curriculum. The discussion includes the effect of external forces upon the optometric profession in the health care delivery system and the type of knowledge the optometrist must have to evaluate certain portions of the health care industry.
Assuntos
Currículo , Optometria/educação , Saúde Pública/educação , Medicina Comunitária/educação , Atenção à Saúde , Docentes de Medicina , Estados UnidosRESUMO
[1-Penicillamine,2-leucine]oxytocin was synthesized by the solid-phase method of peptide synthesis and purified by partition chromatography on Sephadex G-25, followed by gel filtration. The peptide was found to be a very potent competitive inhibitor of oxytocin in the oxytocic assay with a pA2 of 7.14 and an inhibitor of oxytocin in the milk-ejecting assay. The compound showed no agonist activity in either of these assays, and its inhibitory activity at the uterus was of prolonged duration. The 13C nuclear magnetic resonance spectral properties and the 13C T1 (spin-lattice) relaxation times of [Pen1,Leu2]oxytocin were determined, and the results were compared with previous studies of [Pen1]oxytocin, a related competitive inhibitor, and oxytocin, the native hormone agonist. These studies indicated that the hormone inhibitors [Pen1,Leu2]oxytocin and [Pen1]oxytocin have similar conformational and dynamic properties which are different than those of the agonist, oxytocin.
