Subject(s)
Alanine/analogs & derivatives , Cell Wall/drug effects , Dipeptides/chemical synthesis , Alanine/chemical synthesis , Alanine/pharmacology , Bacillus subtilis/drug effects , Dipeptides/pharmacology , Enterococcus faecalis/drug effects , Escherichia coli/drug effects , Klebsiella pneumoniae/drug effects , Microbial Sensitivity Tests , Salmonella typhimurium/drug effects , Staphylococcus aureus/drug effects , Streptococcus pyogenes/drug effectsSubject(s)
Eye Diseases/complications , Mandibulofacial Dysostosis/diagnosis , Adolescent , Cornea/abnormalities , Corneal Ulcer/complications , Dentition , Eye Abnormalities , Female , Humans , Lens Subluxation/complications , Male , Mandibulofacial Dysostosis/complications , Mandibulofacial Dysostosis/diagnostic imaging , Optic Nerve Diseases/complications , RadiographyABSTRACT
2,2-Dimethyl-4-imidazolidinone derivatives of the alpha-amino acids DL-phenylglycine (1), DL-phenylalanine (2), L-tyrosine (3), L-histidine (4), and L-tryptophan (5) were prepared in order to assess their specificity in inhibiting amino acid decarboxylases. Treatment of th alpha-aminonitriles with acetone in the presence of base and heat or treatment of the alpha-amino amides with acetone gave the title compounds in 48-85% yield. The compounds afforded moderate ability to inhibit the decarboxylation of L-phenylalanine, L-tyrosine, or L-histidine in vitro, using crude enzymes. 3 was a better inhibitor of tyrosine decarboxylase (S. faecalis) than 2. 4 and 5 were comparable to 3 in inhibiting tyrosine decarboxylase. 4 was more selective in inhibiting purified histidine decarboxylase (Cl. welchii) than 5, which was inactive. 4 was inactive against fetal rat histidine decarboxylase in vitro.
Subject(s)
Carboxy-Lyases/antagonists & inhibitors , Histidine Decarboxylase/antagonists & inhibitors , Imidazoles/chemical synthesis , Tyrosine Decarboxylase/antagonists & inhibitors , Animals , Clostridium perfringens/enzymology , Enterococcus faecalis/enzymology , Fetus/enzymology , Imidazoles/pharmacology , In Vitro Techniques , Phenylalanine , RatsABSTRACT
Two N-isopropylnorephedrines and their four possible decalol analogs were compared pharmacologically. Four of the six compounds at a concentration of 1 x 10(-4) M caused a potentiation of D(-)-norepinephrine (NE) contraction of the rat vas deferens and increased the maximal response of the preparation to NE. Pretreatment in vivo with reserpine (5 mg/kg ip) 24 hr before the experiment in vitro did not change these effects. At a concentration higher than 1 x 10(-3) M all of the decalin analogs antagonized the effects of NE. All of the analogs lowered the dog blood pressure briefly. The lowering of blood pressure was augmented by alpha-adrenergic blockade and was not changed by beta-adrenergic blockade, atropine, or a ganglionic blocking agent. Tachyphylaxis was not observed. The spontaneous contraction of isolated rabbit atria was depressed by the substances at concentrations of 1 x 10(-4)-1 x 10(-3) M. Catecholamine uptake in rat vas deferens was lowered by the substances and all of them produced a release of catecholamines from vas deferens. By virtue of the conformational rigidity of the decalols, possible inferences concerning the stereochemical aspects of the interaction of the ephedrine analogs with adrenergic neurone-receptor sites are discussed.
Subject(s)
Ethanolamines , Naphthols/pharmacology , Phenethylamines , Receptors, Drug , Animals , Blood Pressure/drug effects , Dogs , Female , In Vitro Techniques , Male , Molecular Conformation , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Myocardial Contraction/drug effects , Naphthols/chemical synthesis , Norepinephrine/metabolism , Norepinephrine/pharmacology , Phenylpropanolamine/analogs & derivatives , Propylamines/pharmacology , Rabbits , Rats , Vas Deferens/drug effects , Vas Deferens/metabolismSubject(s)
Adrenal Cortex Hormones/adverse effects , Cataract/chemically induced , Glaucoma/chemically induced , Keratitis, Dendritic/chemically induced , Adolescent , Adrenal Cortex Hormones/pharmacology , Adrenal Cortex Hormones/therapeutic use , Adult , Child , Eye Diseases/drug therapy , Humans , Intraocular Pressure/drug effects , MaleABSTRACT
Based upon the unpublished finding that 3'-hydroxy-4'-(beta-diethylaminoethoxy)-3',4'-dihydroseselin possessed a potent blood pressure lowering effect in the cat at a dose of 1 mg/kg, the present study examined the activities of several related compounds. These compounds were derived by dissection of the parent compound to give four benzylic ethers of 2-diethylaminoethanol and a diamine, derived by replacing the ether oxygen of the parent compound with an N--CH3 function. The simplest compounds were the benzyl and 2,6-dimethoxybenzyl ethers of the aminoalcohol. Closely related to the benzyl compound was a congener with a hydroxymethyl group on the benzylic carbon. The beta-diethylaminoethyl ether of 4-chromanol was the most complex of the ethers. The blood pressure measurements were carried out on male cats and compared to papaverine hydrochloride as a standard. In all cases, the most potent blood pressure lowering activity resided in the parent compound, which was not greatly superior to the diamine but substantially more active than the other compounds.
