Pharmacology Commons^™

Development Of A Chemical Biology Approach To Uncover The Influence Of Sequence Variations On Ces1 Activity In Live Cells, Samuel James Knebel

Masters Theses

Drug metabolism is the biochemical process of modifying drugs to detoxify and remove them through enzymatic transformations. These biotransformation’s occur primarily in the liver and are critical to understanding how pharmaceutical compounds are chemically altered inside the human body. Human carboxylesterases (CESs) catalyze the hydrolysis of esters, amides, thioesters, and carbamates. CES-mediated hydrolysis plays an important role in the metabolism of many drugs including the first FDA approved antiviral treatment for COVID-19, remdesivir (Veklury), the seizure control medication rufinamide (Banzel), and the flu antiviral drug oseltamivir (Tamiflu). CES activity is known to be influenced by a variety of factors including …

Evaluation Of Α-Pyrrolidindovalerophenone (Α-Pvp) And Its Isomers In Male And Female Sprague-Dawley Rats Trained To Discriminate Mdpv, Kaley Cargile

Masters Theses

Recreational use of synthetic cathinones, 3,4-methylenedioxypyrovalerone (MDPV) and α‐pyrrolidinovalerophenone (α‐PVP), has become increasingly popular, thus prompting characterization of their behavioral and neurochemical effects. MDPV has been studied for several years now, though there is still much unknown about α‐PVP, and its isomers. The primary objective of this study was to characterize the discriminative effects of α‐PVP and its isomers in comparison to MDPV. Male and female Sprague-Dawley rats were trained to discriminate 0.5mg/kg MDPV from saline injections under a fixed ratio 20 (FR 20) schedule of food reinforcement. Substitution tests were conducted with MDPV (0.05-0.5mg/kg), α‐PVP (0.05-0.5mg/kg), (S)-α‐PVP (0.05-1mg/kg) and …

The Effects Of 1, 3, & 7 Trisubstituted And 8-Cyclopentyl Alkylxanthines On Respiration In Newborn Rats, Nathan Creel Davidson

Masters Theses

Methylxanthines have been shown to be promising respiratory stimulants in newborns suffering from recurrent apnea. The respiratory stimulant effects of methylxanthines are most likely due to their antagonism of adenosine receptors. These drugs have been shown to stimulate respiration in newborn rats in doses in excess of 10 mg/kg body weight. Structure-activity studies have shown that methylxanthines not only differ in the antagonism of A₁ and A₂ adenosine receptors but also, as a consequence of their different chemical structures, differ in potency as respiratory stimulants. To assess this, two potent A₁ adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) and …

Identification And Characterization Of Possible Multiple Binding Sites For ((3)H)8-Oh-Dpat In The Hippocampus, Dawna Lea Evans

Masters Theses

No abstract provided.

Fixed-Ratio Size As A Determinant Of The Development Of Tolerance To Morphine, Mark J. Nickel

Masters Theses

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.

Cocaine And Timing: Drug Effects Under A Mixed Fixed-Interval Extinction Schedule, Vincent O. Hodge

Masters Theses

The effects of cocaine hydrochloride (3.2-56.2 mg/kg) were determined in rats performing under a mixed fixed-interval 60-seconds extinction 120-seconds schedule of food delivery. Responses were recorded in successive 5-second bins. With the exception of the highest dose (56.2 mg/kg), cocaine did not significantly affect rate of responding under the fixed-interval component or extinction component, or the time of peak responding under the extinction component. The highest dose significantly reduced response rates and shifted the time of peak responding leftward to quicker and earlier moments. Results are discussed in terms of possible rate- and time-dependent effects of stimulant drugs.

Effects Of Phenobarbital In Combination With Phenytoin Or Valproic Acid On The Delayed-Matching-To-Sample Performance Of Pigeons, Catherine Ann Karas

Masters Theses

The present study examined the effects of phenobarbital (S, 10,20, and 40 mg/kg), phenytoin (2.5, 5, 7.5, and 15 mg/kg), and valproic acid (40, 60, 80, and 120 mg/kg), and those of phenobarbital (10 and 20 mg/kg) in combination with phenytoin (2.5,5, and 7.5 mg/kg) or valproic acid (40, 60, and 80 mg/kg), on the delayed-matching-to-sample performance of pigeons. In general, high doses of each individual drug reduced accuracy. Drug combinations also reduced accuracy relative to control values. Reductions in accuracy produced by drug combinations were very similar in magnitude to those predicted by a response-addition model of drug interaction.

Pathophysiology Of Hemorrhagic Shock And The Protective Effects Of Antioxidants, Annette Elizabeth Fleckenstein

Masters Theses

Considerable attention has focused on the role of free radicals in the pathophysiology of hemorrhagic shock. In this study, four pharmacological mechanisms for antagonizing free radical generation or reactions were compared in terms of their efficacy in attenuating post-hemorrhage (post-reinfusion) cardiovascular collapse. These included blocking arachidonic acid oxidation by cyclooxygenase (eg; ibuprofen), inhibiting superoxide radical production by xanthine oxidase (eg; oxypurinol), chelating iron (eg; desferal), and inhibiting lipid peroxidation (eg; U74006F and U78517G, Upjohn Company, Kalamazoo, Michigan).

Cardiovascular function, cerebral blood flow, arterial blood gases, serum glucose, and plasma vitamin E were examined in a hemorrhage/reperfusion model using urethane-anesthetized rats. …

Reaction Of 2,2,6-Trimethyl-1,3-Dioxin-4-One With Isocyanate Derivatives And The Synthesis Of 2,3,4,6-Tetra-O-Acetyl-Dglucopyranosyl Phenyl Carbodiimide, Tung Van Le

Masters Theses

This research was undertaken to study the synthesis and reactions of isocyanates with diketenes, the synthesis of glycosyl carbodiimide.

The 1,3-oxazine-2,4-dione compounds could be useful in the medicinal chemistry field and the agricultural field, the research using glycosyl carbodiimide as a synthon shows great promise for the medicinal chemistry field.

The Effects Of Xanthine Analogs On Neonatal Rat And Adult Mouse Respiration, Susan M. Reynolds

Masters Theses

Apnea, a prolonged cessation of breathing, is commonly seen in premature infants. This condition, in its severest form, can be lethal and is a suspected cause of sudden infant death syndrome (SIDS). Sometimes referred to as apnea of prematurity, recurrent apnea is presently being treated with respiratory stimulants known as methylxanthines (MX) such as theophylline and caffeine. The benefits of MXs are accompanied by central nervous system stimulation and cardiostimulation which may be detrimental to a premature infant. Theophylline (1,3-diMX) has been shown to produce some of its effects by antagonizing endogenous adenosine. Another xanthine, enprofylline (3-propylxanthine), is presently being …

The Effects Of Various Adenosine And Xanthine Analogues On Mammalian Sperm Motility, Daniel Joseph Cushing

Masters Theses

Caffeine, theophylline, and a number of other xanthine analogues have been shown to stimulate the motility of mammalian spermatozoa. The mechanism by which these compounds act was assumed to be cAMP phosphodiesterase inhibition. However, it has recently been shown that many of the responses elicited by alkylxanthines and their analogues in various tissues are not the result of cAMP phosphodiesterase inhibition but by antagonism of endogenous adenosine. Using the recently described transmembrane migration method this study observed the effect of a number of xanthine and adenosine analogues on mammalian sperm motility. The hypothesis to be tested was that the increase …

Acute Effects Of Phenytoin And Thioridazine, Alone And Combination, Upon Water Intake And Body Weight Changes In Rats, Miriana Witzig-Krstic

Masters Theses

Concommitant medication of anticonvulsants and psychotropics appears to be predominant among mentally retarded, geriatric, and psychiatric in- and out-patient populations. Despite suggested interaction and toxicity resulting from such combination treatment, substantial data remains unavailable. This study was designed to explore effects of dual treatment of thioridazine

Analogues Of Steffimycinone, David Wayne Elrod

Masters Theses

Several analogues of Steffimycinone - an anthracycline antitumor antibiotic - have been prepared. Modifications were made at C-7 and C-10 of the non-aromatic A ring portion of the anthracycline nucleus. Compounds with nitrogen substituents were prepared. The synthesis of these compounds is discussed as well as their antitumor activity. The unsuccessful approaches to several other analogues are also discussed.

Production Of Acute Duodenal Ulcers In Rats By Infusion Of Gastric Secretogogues, Thomas John Stout

Masters Theses

Antibiotic Potential In The Liverworts, Especially Ricciocarpus Natans (L.) And Marchantia Polymorpha (L.), Theodore Roy Shields

Masters Theses

No abstract provided.