Challenges of drug development during the COVID-19 pandemic: Key considerations for clinical trial designs.

There is an urgent need for targeted and effective COVID-19 treatments. Several medications, including hydroxychloroquine, remdesivir, lopinavir-ritonavir, favipiravir, tocilizumab and others have been identified as potential treatments for COVID-19. Bringing these repurposed medications to the public for COVID-19 requires robust and high-quality clinical trials that must be conducted under extremely challenging pandemic conditions.

Symptomatic relief of botulinum neurotoxin/a intoxication with aminopyridines: a new twist on an old molecule.

Botulinum neurotoxins (BoNT) are the etiological agents responsible for botulism, a disease characterized by peripheral neuromuscular blockade and a characteristic flaccid paralysis of humans. BoNT/A is the most toxic protein known to man and has been classified by the Centers of Disease Control (CDC) as one of the six highest-risk threat agents for bioterrorism. Of particular concern is the apparent lack of clinical interventions that can reverse cellular intoxication.

The effect of commonly used vehicles on canine hematology and clinical chemistry values.

Drug metabolism and pharmacokinetic (DMPK) studies are an important phase in drug discovery research. Compounds are administered via the intravascular or extravascular routes to animals to calculate various pharmacokinetic parameters. An important step in this process is dissolving the novel compound in a safe vehicle.

Dominant-submissive behavior as models of mania and depression.

This review examines the ways in which dominant-subordinate behavior in animals, as determined in laboratory studies, can be used to model depression and mania in humans. Affective disorders are mood illnesses with two opposite poles, melancholia (depression) and mania that are expressed to different degrees in affected individuals. Dominance and submissiveness are also two contrasting behavioral poles distributed as a continuum along an axis with less or more dominant or submissive animals.

Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model.

The present study tests the activity of nootropic drugs in a behavioral test linked to depression. This test measures the reduction of submissive behavior in a competition test as the relative success of two food-restricted rats to gain access to a feeder. Nootropic drugs tested include piracetam (2-oxo-1-pyrrolidineacetamide), aniracetam (1-(4-methoxybenzoyl)-2-pyrrolidinone), the Ampakine, Ampalex, 1-(quinoxalin-6-ylcarbonyl)piperidine, and analogs were compared to the antidepressants, fluoxetine ((+/-)-N-methyl-gamma-(4-[trifluoromethyl]phenoxy)-benzenepropanamine) and desimpramine (5H-dibenz[b,f]azepine-5-propanamine, 10,11-dihydro-N-methyl-, monohydrochloride), while the anxiolytic diazepam (7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2(1H)-one) served as a control.

Reduction of submissive behavior in rats: a test for antidepressant drug activity.

Randomly paired rats were food deprived overnight and placed in an apparatus compelling them to compete for a food reward. About half of these pairs developed a dominant-submissive relationship measured as a significant difference in time spent on the feeder by each rat. This relationship developed over a 2-week period and remained stable for at least the next 5 weeks.