ABSTRACT
Bone injury inflicted at varying time intervals during 24 hr day-night cycle caused significant varying increase in plasma 17-OHCS levels in all traumatized animals and the levels remained elevated up to 24 hr after trauma. The level of plasma 17-OHCS was found to be aberrated in all the traumatized animals. Thus, adequate adrenocortical response to trauma and aberration in the adrenocortical secretory activity appears inevitable irrespective of the time at which the trauma is produced. However, the degree of response depends on the particular time at which the trauma is inflicted.
Subject(s)
17-Hydroxycorticosteroids/blood , Bone and Bones/injuries , Circadian Rhythm , Animals , Female , Femoral Fractures/blood , Fractures, Closed/blood , Male , RabbitsABSTRACT
Ribonucleoside diphosphate reductase (RDR) inhibitory activity of 2-formylpyridine and 1-formylisoquinoline thiosemicarbazones is quantitatively analysed in relation to a steric parameter (van der Waals volume, VW) and the hydrophobic parameter logP. The activity is found to be significantly correlated with VW and very poorly with logP. On the basis of this, it is inferred that RDR inhibition by thiosemicarbazones is very sensitive to steric effects and is little influenced by the hydrophobic character of the molecules.
Subject(s)
Ribonucleoside Diphosphate Reductase/antagonists & inhibitors , Ribonucleotide Reductases/antagonists & inhibitors , Thiosemicarbazones/pharmacology , Chemical Phenomena , Chemistry, Physical , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Attempts have been made to correlate hyperthermic potencies in rabbits and LSD-like effect in rat of a series of phenylisopropylamines (amphetamines) with physico-chemical parameters. In case of 2,4,5-trisubstituted analogs, hyperthermic potencies are found to be well correlated parabolically with the hydrophobic parameter pi. However, for the same series, the LSD-like effect is found to be related with pi in combination of steric parameter of 4-substituent. It is therefore inferred that hyperthermia in rabbit may be the function only of the hydrophobic character of molecule, but the LSD-like effect is influenced by the steric hindrance of 4-substituent also.
Subject(s)
Amphetamines/pharmacology , Hallucinogens/pharmacology , DOM 2,5-Dimethoxy-4-Methylamphetamine/pharmacology , Animals , Body Temperature/drug effects , Chemical Phenomena , Chemistry, Physical , Lysergic Acid Diethylamide/pharmacology , Rabbits , Rats , Structure-Activity RelationshipABSTRACT
An attempt is made to analyse the serotonin receptor binding affinity (pD2) of a small series of hallucinogenic phenylalkylamines in relation to various physical and physico-chemical parameters. It is found that pD2 can be significantly correlated with steric parameters, such as van der Waals (Vw) and molar refraction (MR). Based on the correlation equations obtained, it is suggested that the hallucination might be related with binding of drug with the serotonin receptor and that such binding might involve a van der Waals type of interaction.
Subject(s)
Amines/pharmacology , Hallucinogens/pharmacology , Receptors, Serotonin/drug effects , Binding Sites/drug effects , Chemical Phenomena , Chemistry, Physical , Regression AnalysisABSTRACT
The nature of the substituents and their contribution at different ring positions to the overall hallucinogenic activity in a series of phenylalkylamines (amphetamines) are studied by using Fujita-Ban additive model. The calculated activity contributions of substituents and of parent structure, respectively, are then utilized to predict the most potent compound in the series and to remove the uncertainties in the observed activity of some phenylalkylamines. The most potent compound predicted is 2,6-dimethoxy-4-bromophenylisopropylamine.
Subject(s)
Amines/pharmacology , Hallucinogens , Mescaline/analogs & derivatives , Mescaline/pharmacology , Models, Biological , Structure-Activity RelationshipABSTRACT
Attempt is made to correlate the hallucinogenic activity of a series of mescaline analogs with Kier's molecular connectivity index (chi). In order to find a simpler and more meaningful correlation, a little modification is suggested to the first-order valence connectivity index (1 chi upsilon). The modification is found to reveal utterly simple but significant correlations between activity and 1 chi upsilon, which could describe the structural influence on the activity more vividly.
Subject(s)
Hallucinogens , Mescaline/analogs & derivatives , Chemical Phenomena , Chemistry, Physical , Mescaline/pharmacology , Phenethylamines/pharmacology , Structure-Activity RelationshipABSTRACT
A study is made on the correlations of inhibitory activity of a series of tryptamine derivatives on serotonin uptake in thrombocyte with van der Waals volume (Vw). Bearing significant correlations, the compounds were separated into two distinct groups to conform the suggestion that two receptor sites of a sterically dissimilar nature may be involved in serotonin uptake and its inhibition. And on the basis of significance of the correlation, it was further sought to suggest that to act as inhibitors the compounds must possess the structural resemblance with serotonin at least while complexing with receptor sites.
Subject(s)
Serotonin Antagonists/pharmacology , Serotonin/metabolism , Tryptamines/pharmacology , Binding, Competitive , Blood Platelets/metabolism , Chemical Phenomena , Chemistry, Physical , In Vitro Techniques , Receptors, Serotonin , Structure-Activity RelationshipABSTRACT
A quantitative analysis is made on the relationship of vasodilator activity of adenosine analogs with Kier's molecular connectivity (chi) and van der Waals volume (Vw). In all attempts the most significant correlation that surfaced led to suggest that molecular shape and size of the molecules would be important in their vasodilator activity.
Subject(s)
Adenosine/analogs & derivatives , Vasodilator Agents , Adenosine/pharmacology , Animals , Chemical Phenomena , Chemistry, Physical , Dogs , Molecular Conformation , Structure-Activity RelationshipABSTRACT
The anesthetic potencies of halogenated hydrocarbons are found by the regression analysis to have a fairly good correlation with boiling point and first-order valence molecular connectivity (1 chi v). Also a significant correlation is found between boiling point and 1 chi v themselves.
Subject(s)
Anesthetics , Hydrocarbons, Halogenated/pharmacology , Chemical Phenomena , Chemistry, Physical , Molecular Conformation , Structure-Activity RelationshipABSTRACT
The cellular respiratory inhibition activity of 7-substituted 4-hydroxyquinoline-3-carboxylic acids recently designed by Shah and Coats is found by regression analysis to be significantly correlated with van der Waals volume (V(w)). A parabolic correlation is obtained in case of ascites cell inhibition and a linear correlation in case of malate dehydrogenase inhibition. The correlation of both types of inhibition with a single parameter, V(w), makes the process of substituent selection in designing more potent inhibitors of whole respiratory cell much simpler.
