Episode #125 of the Stack Overflow podcast is here. We talk Tilde Club and mechanical keyboards. Listen now
6

Specific parts — moieties — of an agonist molecule bind to the receptor protein, causing the receptor to change shape, which in turn initiates a signaling pathway inside the cell. Some agonists are better at causing the receptor to change to its "optimal shape" for relaying signal. These are called "full agonists". Other agonists cause a partial change in ...


4

The reason is to make it easier to determine a suitable dose from the graph. Normally, using a arithmetic scale, the response curve is a hyperbolic, with most of the information squished together in a small section of the graph. By using the log the function usually becomes somewhat sigmoid, with a relatively linear section in the transition from low-high ...


3

Does the ingestion of alcohol, when taking (racemic) methylphenidate can actually make it more potent? It is the 2011 study you've mentioned that answers most of the question. In the study, ethanol co-ingestion with racemic MPH elevated maximal plasma levels of d-MPH by up to 40%. The participants reported greater stimulant effect after alcohol + MPH than ...


3

Short answer: Yes. Slightly longer answer: Recall how a vaccine works - it introduces an antigen to the body, which provokes the body to produce antibodies towards that antigen. Antibodies, simply explained, call upon the remainder of the immune system to fight off a potential infection of foreign body. If there is no immune system to mobilize, the ...


3

MD is used for studying structural changes. Simulation of biochemical pathways involves the kinetics (you are not really looking at how enzyme structure changes when it binds to substrate). You can certainly pool all the modelling strategies together to make a hybrid multiscale model. There are many people who work on such kind of modelling approaches. You ...


3

Yes. The antibiotic (general microorganism “targeter”) you’re looking for is an antifungal. There are fewer ways to target fungi as opposed to bacteria, but we can target them nonetheless. The fungal cell membrane has ergosterol to regulate its permeability whereas the mammalian cell relies on cholesterol. Fungi have cell walls which are not present in ...


3

The process of downregulating a receptor by internalizing and degrading it in response to (sometimes prolonged) activation or (sometimes prolonged) failure to activate is what pharmacologists call desensitization (in either context). You can read about this generally in Goodman and Gilman's Pharmacological Basis of Therapeutics, Chapter 3, under the ...


3

Resistance to antiviral therapy is a problem in the treatment of many viral illnesses. Influenza is particularly significant given the epidemiological characteristics of the disease. This Nature Medicine article gives a good overview of oseltamivir resistant pandemic H1N1, which is a useful example, since our assumption that resistant virus would not ...


3

It's not that people didn't want to use hemagglutinin as a target for antivirals, it's that they haven't been able to get the antivirals through the approval process yet. There are a number of experimental inhibitors (see for example Progress of small molecular inhibitors in the development of anti-influenza virus agents) but the approval and licensing ...


2

Short Answer You might be interested in learning about telomeres, telomerase, and telomerase gene therapy. For example, Boccardi & Herbig (2012): describe a mouse study in which they used telomerase gene therapy to improve the healthspan and lifespan of mice by up to 24%. As far as I know, we have no successful human trials of similar therapies that ...


2

Partial Answer and Suggestions As @De_Novo says, this is a complicated, albeit very interesting, question. There are various reasons for this, such as the fact that the receptors aren't just internalised but also recycled and the fact that there may be antagonist and dose-dependent changes in receptor internalisation. There's the added complexity that ...


2

VEGF is a family of growth factors that promote angiogenesis and vasculogenesis. Vascularization is a key step in the progression of cancer, so the VEGF family has often been a target for suppression: preventing vascularization of tumors can stop their further growth. That said, your premise that VEGF hasn't been tried clinically is false: there have been ...


2

Reverse use dependence is the reduction of a drug's efficacy with the repeated use of the target. This contrasts with ordinary use dependence, for instance with $\mathrm{Na}^+$ blocking local anaesthetics, where they exert more block after tissue use. Reverse use dependence is particularly (but not exclusively) seen with channel blockers such as quinidine. ...


1

The first box contains Tegretol Retard, which is an old name for what is now known as Tegretol Prolonged Release (medicines.org.uk). The second box contains Tegretol CR, which means controlled-release (PubMed). Drugs.com says: Your medicine is called Tegretol 200mg prolonged-release Tablets/Tegretol CR 200mg Tablets or Tegretol 400mg prolonged-release ...


1

No, absence of an stimulating substance is not appropriate to consider as inhibition. To see why, consider a situation where there are two such substances, substance A and substance B, which can both stimulate protein P (many such relations exist). If you add only substance B, then protein P will be stimulated. Since P is being stimulated in this case, it ...


1

I think you are confusing potency with receptor affinity. The (unsourced) numbers you indicate appear to be DEA-style "potency", which probably refer to the effective dose (of some kind). The fentanyl to morphine ratio on the κ-opioid receptor affinity, from human studies is only 1.35 to 1.14 (on average). In contrast the N-methyl fentanyl is estimated ...


1

When a tumor is removed from a patient, it is usually send to the pathology the make sure that it has been excised completely to make sure there are no residues. Often this tumor is also used to analyze the mutation status of the tumor to determine, which further treatment is possible. For example, this is routinely done for melanoma where the mutation ...


1

Keeping in mind that this was a very small, not especially well-controlled preliminary/exploratory study. Because life expectancy was increased by ~2.5 years - or got ~2.5 years younger biologically, depending on how you look at - it is the reason that this study is being talked about at all. In the TRIIM study 9 men, ages 51-65, first took hGH alone (0....


1

Not within the next two decades, at least (assuming you meant nearly total reversal of the effects of physiological aging). Any further than that is impossible to predict, since we are likely only a few breakthroughs away at this point (however, with extremely bad luck, these could take centuries to achieve, since presumably no scientist knows the 'optimal ...


1

What are CYPs? How are they different from other enzymes? Cytochrome P450 enzymes (CYPs) are a large family of enzymes involved in the metabolism of many endogenous and exogenous compounds (including typical dietary substances and pharmaceuticals). There are many different CYPs, each individual CYP form can metabolize many different compounds, and a single ...


1

I think the OP is asking the following: If an enzyme is not specific one substrate, but is simultaneously presented with a pair of substrates, which one 'wins' and how do we decide? For example, if an enzyme is presented with a racemate such that the D-form has a 10-fold lower $K_m$ than the L-form, but the L-form has a 5-fold higher $k_{cat}$, which ...


1

I am not an expert on HIV but I am answering based on general principles. This is a typical example of selection of individuals/populations with different fitness. Reversion to wild-type (WT) would happen if the WT has higher fitness in that environment. Assuming that WT is the fittest under drug-free conditions, it is not difficult to understand that the ...


1

Good question, but first I'll address a note in the comments. In bronchial smooth muscle, do β2 receptors receive sympathetic innervation? Canning and Fischer (2001) claim that bronchial smooth muscle do receive sympathetic innervation. But it would still be correct to say that β2 expression plays little role in regulating smooth muscle tone in the human ...


1

The short answer is that an inverse agonist binds preferentially to the inactive state of the receptor, so it reduces the receptor's intrinsic, basal activity. The agonist was only raising the activity, not switching it on. The most basic model of receptor pharmacology is that the receptor, $\ce{R}$, and the agonist, $\ce{A}$, are in a chemical equilibrium: ...


Only top voted, non community-wiki answers of a minimum length are eligible