tag:blogger.com,1999:blog-37148773.post8180422977996306694..comments2024-03-27T14:50:47.345-04:00Comments on <center>Sandwalk</center>: Monday's Molecule #152Larry Moranhttp://www.blogger.com/profile/05756598746605455848noreply@blogger.comBlogger10125tag:blogger.com,1999:blog-37148773.post-81915698218034608312011-12-07T20:34:58.177-05:002011-12-07T20:34:58.177-05:00That doesn't appear to be true from reading th...<i>That doesn't appear to be true from reading the scientific literature</i><br /><br />I was late to this party and in any way had no idea what the molecule is (other than that it's a drug as indicated by chlorine atom). So for educational purposes I looked up in pubmed what thiazides do and it sure appears to be true that their main mechanism of action is inhibition of NCC. In fact, a synonym for NCCT, where T stands for thiazide-sensitive. NCC null results in the <a href="http://en.wikipedia.org/wiki/Gitelman_syndrome" rel="nofollow">Gitelman syndrome</a>, with all the same symptoms as chlorothiazide effects (except, of course, on a different scale). To the contrary, virtually nothing in the literature on carbonic anhydrase inhibitors suggests that thiazides act through it.DKnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-59558550315309338132011-12-07T16:53:26.476-05:002011-12-07T16:53:26.476-05:00DK says,
Chlorothiazide as carbonic anhydrase inh...DK says,<br /><br /><i>Chlorothiazide as carbonic anhydrase inhibitor is an outdated 1950s research. The consensus from later work indicates that its main mechanism of action is inhibition of NaCl transporter. </i><br /><br />That doesn't appear to be true from reading the scientific literature but it's often hard to tell what the consensus is unless you're on the inside.<br /><br />Part of the problem seems to be that there are many isozymes of carbonic anhydrase. Only one was known in the 1950s but now there are 12 of them and some are involved in regulating ion pumps in the kidney.Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-15289600330644450472011-12-07T12:06:56.727-05:002011-12-07T12:06:56.727-05:00Chlorothiazide as carbonic anhydrase inhibitor is ...Chlorothiazide as carbonic anhydrase inhibitor is an outdated 1950s research. The consensus from later work indicates that its main mechanism of action is inhibition of NaCl transporter.DKnoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-52882147296479150262011-12-07T09:33:46.130-05:002011-12-07T09:33:46.130-05:00Patience, Alex, patience. I need time to check out...Patience, Alex, patience. I need time to check out your answer.Larry Moranhttps://www.blogger.com/profile/05756598746605455848noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-11618211938570924732011-12-06T18:58:33.147-05:002011-12-06T18:58:33.147-05:00No winner? :(No winner? :(Alexhttps://www.blogger.com/profile/02590604089043425452noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-10181646759075688222011-12-06T17:04:34.471-05:002011-12-06T17:04:34.471-05:00http://en.wikipedia.org/wiki/Hydrochlorothiazide
...http://en.wikipedia.org/wiki/Hydrochlorothiazide<br /><br />Took me a while to hunt it down and you already have winners. So I won't bother a further reply.<br /><br />Thanks, it tested my memory from my 30 year old BioChem days...Georgenoreply@blogger.comtag:blogger.com,1999:blog-37148773.post-8669464043233545422011-12-05T22:15:27.157-05:002011-12-05T22:15:27.157-05:00"Chlorothiazide"
6-chloro-1,1-dioxo-2H-1..."Chlorothiazide"<br />6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide<br />(This is named as a sulfonamide, as opposed to a heterocyclic ring...apparently.)<br /><br />It's a diuretic, and may be used to lower blood pressure by causing excretion of excess fluids.<br /><br />It works by inhibiting Na-Cl symporters in the distal tubules in the kidneys, inhibiting reabsorsion Na and Cl from the urine, and by osmosis, increasing loss of water to the urine.<br /><br />I wasn't able to find anything on the inhibitory mechanism.Christopher Yauhttps://www.blogger.com/profile/00359246621463321318noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-3023361962693378782011-12-05T22:14:39.770-05:002011-12-05T22:14:39.770-05:00"Chlorothiazide"
6-chloro-1,1-dioxo-2H-1..."Chlorothiazide"<br />6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide<br />(This is named as a sulfonamide, as opposed to a heterocyclic ring...apparently.)<br /><br />It's a diuretic, and may be used to lower blood pressure by causing excretion of excess fluids.<br /><br />It works by inhibiting Na-Cl symporters in the distal tubules in the kidneys, inhibiting reabsorsion Na and Cl from the urine, and by osmosis, increasing loss of water to the urine.<br /><br />I wasn't able to find any information on it's inhibitory mechanism.Christopher Yauhttps://www.blogger.com/profile/00359246621463321318noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-10761894269840403942011-12-05T20:29:44.981-05:002011-12-05T20:29:44.981-05:00Chlorothiazide or 6-chloro-1,1-dioxo-2H-1,2,4-benz...Chlorothiazide or 6-chloro-1,1-dioxo-2H-1,2,4-benzothiadiazine-7-sulfonamide. It is an inhibitor of carbonic anhydrase, an enzyme which in the kidney normally acts to create bicarbonate and protons from carbon dioxide and water. The proton gradient created from this is normally used to reabsorb sodium ions from urine via the Na+/H+ antiporter. Moreover, chlorothiazide also interferes with the Na+/Cl- symporter. Administration of chlorothiazide interferes with these processes in the kidney and therefore creates a saluretic effect (salt excretion into urine), which is useful for conditions such as hypertension.<br /><br />It's also part of a family of antibiotics (sulfonamides, function self-evident), which interfere with bacterial synthesis of folate by dihydropteroate synthetase. I think you've done a Monday Molecule on prontosil (which I believe I won), but I've summarised both possible answers here.<br /><br />My name is 凌嘉誠.Alexhttps://www.blogger.com/profile/02590604089043425452noreply@blogger.comtag:blogger.com,1999:blog-37148773.post-71700701840004221762011-12-05T17:41:57.040-05:002011-12-05T17:41:57.040-05:00IUPAC: 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfon...IUPAC: 6-chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide<br /><br />AKA ChlorothiazideJoseph C. Somodynoreply@blogger.com