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DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai) , INDIA 36Yrs Exp. in the feld of Organic Chemistry,Working for AFRICURE PHARMA as ADVISOR earlier with GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google, NO ADVERTISEMENTS , ACADEMIC , NON COMMERCIAL SITE, world acclamation from industry, academia, drug authorities for websites, blogs and educational contribution, ........amcrasto@gmail.com..........+91 9323115463, Skype amcrasto64 View Anthony Melvin Crasto Ph.D's profile on LinkedIn Anthony Melvin Crasto Dr.

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DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA, ROW2TECH, NIPER-G, Department of Pharmaceuticals, Ministry of Chemicals and Fertilizers, Govt. of India as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

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Recent Posts

Neuroprotective effects of Asiaticoside – a Saponin of Centella asiatica

August 17, 2014 3:13 am / Leave a comment


Ralph Turchiano's avatarCLINICALNEWS.ORG

PUBLIC RELEASE DATE:

10-Aug-2014

In the central nervous system, Asiaticoside has been shown to attenuate in vitro neuronal damage caused by exposure to β-amyloid. However, its potential neuroprotective properties in glutamate-induced excitotoxicity have not been fully studied. Researchers from Fourth Military Medical University of Chinese PLA, China reported that pretreatment with Asiaticoside decreased neuronal cell loss in a concentration-dependent manner and restored changes in expression of apoptotic-related proteins Bcl-2 and Bax. Asiaticoside pretreatment also attenuated the upregulation of NR2B expression, a subunit of N-methyl-D-aspartate receptors, but did not affect expression of NR2A subunits. Additionally, in cultured neurons, Asiaticoside significantly inhibited Ca2+ influx induced by N-methyl-D-aspartate. Their results provide a new insight into the neuroprotective effects of Asiaticoside. The relevant study has been published in the Neural Regeneration Research (Vol. 9, No. 13, 2014).

View original post 85 more words

Lipid Metabolism

August 17, 2014 3:10 am / Leave a comment


larryhbern's avatarLeaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

Lipid metabolism

Larry H. Bernstein, MD, FCAP, Reporter and Curator

Leaders in Pharmaceutical Intelligence

http://pharmaceuticalintelligence.com/8-10-2014/Lipid_metabolism

This is fourth of a series of articles, lipid metabolism, that began with signaling and signaling pathways. These discussion lay the groundwork to proceed in later discussions that will take on a somewhat different approach. These are critical to develop a more complete point of view of life processes.  I have indicated that many of the protein-protein interactions or protein-membrane interactions and associated regulatory features have been referred to previously, but the focus of the discussion or points made were different.  The role of lipids in circulating plasma proteins as biomarkers for coronary vascular disease can be traced to the early work of Frederickson and the classification of lipid disorders.  The very critical role of lipids in membrane structure in health and disease has had much less attention, despite the enormous importance, especially in…

View original post 10,510 more words

THE GROWING IMPACT OF CLICK CHEMISTRY ON DRUG DISCOVERY

August 16, 2014 3:37 am / 1 Comment on THE GROWING IMPACT OF CLICK CHEMISTRY ON DRUG DISCOVERY


 

The growing impact of click chemistry on drug discovery

HC Kolb, KB Sharpless – Drug discovery today, 2003 – Elsevier

Click chemistry is a modular approach that uses only the most practical and reliable
chemical transformations. Its applications are increasingly found in all aspects of drug
discovery, ranging from lead finding through combinatorial chemistry and target-templated …
 
Click chemistry is a modular approach that uses only the most practical
and reliable chemical transformations. Its applications are increasingly
found in all aspects of drug discovery, ranging from lead finding through
combinatorial chemistry and target-templated in situchemistry, to proteomics
and DNA research, using bioconjugation reactions. The copper-(I)-catalyzed
1,2,3-triazole formation from azides and terminal acetylenes is a particularly
powerful linking reaction, due to its high degree of dependability, complete
specificity, and the bio-compatibility of the reactants. The triazole products
are more than just passive linkers; they readily associate with biological
targets, through hydrogen bonding and dipole interactions.
 
 
 

GET YOUR PDF AT

http://image.sciencenet.cn/olddata/kexue.com.cn/blog/admin//images/upfiles/2007101622257911935.pdf

The growing impact of click chemistry on drug discovery

 

 

 

 

Higher-Order Structure Comparability: Case Studies of Biosimilar Monoclonal Antibodies

August 16, 2014 3:03 am / 1 Comment on Higher-Order Structure Comparability: Case Studies of Biosimilar Monoclonal Antibodies


141206AR03_O_F0001g

Figure 1a: Diagram of the antibody array enzyme-linked immunosorbent assay (ELISA)

141206AR03_O_F0002g

Figure 1b: ELISA format for the antibody array technology

Great successes for monoclonal antibody (MAb)–based biologics over the past decade have provided many valuable options for patients combating some of the most serious diseases in the world, including cancer and autoimmune diseases. MAbs and antibody–drug conjugates (ADCs) are among the fastest growing biologic segments in development, with hundreds of candidates currently under clinical study.

read at

http://www.bioprocessintl.com/manufacturing/biosimilars/higher-order-structure-comparability/

 

Macrocycles in new drug discovery

August 15, 2014 2:33 pm / 1 Comment on Macrocycles in new drug discovery


Macrocycles in new drug discovery

Jamie Mallinson, Ian Collins

Future Medicinal Chemistry, Jul 2012, Vol. 4, No. 11, Pages 1409-1438.

Summary | Full Text | PDF (3354 KB) | PDF Plus (3440 KB) | Add to Favorites | Related 

http://www.future-science.com/doi/full/10.4155/fmc.12.93?src=recsys

The use of drug-like macrocycles is emerging as an exciting area of medicinal chemistry, with several recent examples highlighting the favorable changes in biological and physicochemical properties that macrocyclization can afford. Natural product macrocycles and their synthetic derivatives have long been clinically useful and attention is now being focused on the wider use of macrocyclic scaffolds in medicinal chemistry in the search for new drugs for increasingly challenging targets. With the increasing awareness of concepts of drug-likeness and the dangers of ‘molecular obesity’, functionalized macrocyclic scaffolds could provide a way to generate ligand-efficient molecules with enhanced properties. In this review we will separately discuss the effects of macrocyclization upon potency, selectivity and physicochemical properties, concentrating on recent case histories in oncology drug discovery. Additionally, we will highlight selected advances in the synthesis of macrocycles and provide an outlook on the future use of macrocyclic scaffolds in medicinal chemistry.

Drug discovery: a view through the looking glass

August 15, 2014 2:28 pm / 1 Comment on Drug discovery: a view through the looking glass


 
Liposome microarray technology is a new solution to the growing costs of drug discovery [1]. As numerous blockbuster drugs’ patents expire and regulatory requirements for new drugs tighten, the future for drug discovery begins to look rather uncertain. For example, through 2015, biologic drugs worth more than US$80 billion in global sales will lose patent protection
 
Drug discovery: a view through the looking glass

Steven Lenhert, Franklin G Vellanti

Future Medicinal Chemistry, Oct 2012, Vol. 4, No. 16, Pages 2011-2013.

Citation | Full Text | PDF (1063 KB) | PDF Plus (1071 KB) |

http://www.future-science.com/doi/full/10.4155/fmc.12.125?src=recsys

Drug discovery: Past and present

August 15, 2014 2:20 pm / Leave a comment


 

 

The field of biotechnology has revolutionized the drug discovery process. Recombinant DNA-driven drug discovery process is beginning to add new avenues for some old drugs. In its infancy, genetic engineering was considered useful only for the production of therapeutic proteins. Insulin, for example, previously prepared by isolation of pancreatic tissue of bovine or porcine species, can now be prepared identical to human insulin by biotechnology. Companies like Genentech and Biogen were founded solely with this objective. However, proteins do not make ideal drugs, being difficult to administer, rapidly cleared, and potentially immunogenic. Despite these disadvantages, a rapidly increasing number of “biopharmaceuticals” including recombinant proteins, therapeutic monoclonal antibodies, and even antisense oligonucleosides have been approved for indications ranging from metastatic breast cancer (Herceptin) to rheumatoid arthritis (Remicade, Enbrel).

 

READ AT

Giridhar R. Drug discovery: Past and present. J Adv Pharm Technol Res 2012;3:2

 

Giridhar R. Drug discovery: Past and present. J Adv Pharm Technol Res [serial online] 2012 [cited 2014 Aug 15];3:2. Available from: http://www.japtr.org/text.asp?2012/3/1/2/93554

HALOPERIDOL

August 15, 2014 2:10 pm / Leave a comment


Haloperidol3DanJ.gif

 

 

 

Haloperidol /hæloʊpɛridɒl/ (INN, BAN, USAN, AAN; most common brand names: Haldol, Serenace) is an antipsychotic medication used in the treatment of schizophrenia, acute psychosis, mania, delirium, tics in Tourette syndrome, choreas, nausea and vomiting inpalliative care, intractable hiccups, agitation and severe anxiety.[3][4][5] Haloperidol is a butyrophenone derivative and functions as aninverse agonist of dopamine. It is classified as a typical antipsychotic and has pharmacological effects similar to the phenothiazines.[4]

A long-acting decanoate ester of haloperidol is used as an injection given every four weeks to people with schizophrenia or related illnesses who have poor adherence to medication regimens (most commonly due to them forgetting to take their medication, or due to poor insight into their illness) and suffer frequent relapses of illness, or to overcome the drawbacks inherent to its orally administered counterpart.[6] Such long acting injections are controversial because it can be seen as denying people their right to stop taking their medication.

It is on the World Health Organization’s List of Essential Medicines, a list of the most important medication needed in a basic health system.[7]

Skeletal formula of haloperidol decanoate: The decanoate group is highlighted in blue.

 

Brief background information

Salt ATC Formula MM CAS
– N05AD01 C 21 H 23 ClFNO 2 375.87 g / mol 52-86-8

Application

  • neuroleptic
  • antidiskinetik
  • antipsychotic
  • dopamine antagonists

Classes of substances

  • Chloro alcohols
    • p-Ftorbutirofenony 4-piperidinyl derivatives
      • Piperidinol

Synthesis pathway

Synthesis a)


Trade Names

Country Trade name Manufacturer
Germany Haldol-Janssen Janssen-Cilag
various generic drugs
France Haldol Janssen-Cilag
United Kingdom – “- – “-
Serenak Ivax
Italy Haldol Janssen-Cilag
Serenas Lusofarmaco
Japan Galomont Janssen – Dainippon Sumitomo
Neoperidol Janssen
Serenak Dainippon Sumitomo
USA various generic drugs
Ukraine Haloperidol Ltd. “Gedeon Richter”, Hungary
various generic drugs

Formulations

  • ampoules of 5 mg / 1 ml, 100 mg / ml, 50 mg / ml;
  • drops of 2 mg to 20 mg / ml, 2 mg / ml, 0.5 mg / ml;
  • garnuly 1%;
  • Powder 1%;
  • 0.2% solution, 10 mg;
  • oral solution 2 mg / ml, 10 mg / ml;
  • Tablets of 0.75 mg, 1 mg, 1.5 mg, 2 mg, 3 mg, 5 mg, 10 mg, 20 mg

Links

  • Janssen, PAJ et al .: J. Med. Pharm. Chem. (JMPCAS) 1, 281 (1959).
  • DE 1289845 (Janssen; appl. 18/4/1959; GB -prior. 4.22.1958).
  • US 3,438,991 (Janssen; 4.15.1969; GB -prior. 18.11.1959).

 

1H NMR

13 C NMR

IR

 

 

 

MASS

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-40422012000200028

Systematic (IUPAC) name
4-[4-(4-Chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one
Clinical data
Trade names Haldol
AHFS/Drugs.com monograph
MedlinePlus a682180
Pregnancy cat. C (AU) C (US)
Legal status Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)
Routes Oral, IM, IV, depot (asdecanoate ester)
Pharmacokinetic data
Bioavailability 60-70% (Oral)[1]
Protein binding ~90%[1]
Metabolism Liver-mediated[1]
Half-life 14-26 hours (IV), 20.7 hours (IM), 14-37 hours (oral)[1]
Excretion Biliary (hence in faeces) and in urine[1][2]
Identifiers
CAS number 52-86-8 Yes
ATC code N05AD01
PubChem CID 3559
IUPHAR ligand 86
DrugBank DB00502
ChemSpider 3438 Yes
UNII J6292F8L3D Yes
KEGG D00136 Yes
ChEBI CHEBI:5613 Yes
ChEMBL CHEMBL54 Yes
Chemical data
Formula C21H23ClFNO2 
Mol. mass 375.9 g/mol

History

Haloperidol was discovered by Paul Janssen.[70] It was developed in 1958 at the Belgian company Janssen Pharmaceutica and submitted to the first of clinical trials in Belgiumlater that year.[71]

Haloperidol was approved by the U.S. Food and Drug Administration (FDA) on April 12, 1967; it was later marketed in the U.S. and other countries under the brand name Haldol byMcNeil Laboratories.[citation needed]

Society and culture

Coincident with civil unrest in the United States in the 1960s and 1970s, schizophrenia was racialized to match the behavior of angry/violent black men. Haldol was promoted as a way to pacify them, and was marketed to appeal to feelings of racial unease. (cf. Metzl 2010. The Protest Psychosis)

Soviet dissidents, including medical staff, have reported several times on the use of haloperidol in the Soviet Union for punitive purposes or simply to break the prisoners’ will.[72][73][74] Notable dissidents who were administered haloperidol as part of their court-ordered treatment were Sergei Kovalev and Leonid Plyushch.[75] The accounts Plyushch gave in the West, after he was allowed to leave the Soviet Union in 1976, were instrumental in triggering Western condemnation of Soviet practices at the World Psychiatric Association‘s 1977 meeting.[76] The use of haloperidol in the Soviet Union’s psychiatric system was prevalent because it was one of the few psychotropic drugs produced in quantity in the USSR.[77]

Haloperidol has been used for its sedating effects during the deportations of immigrants by the United States Immigration and Customs Enforcement (ICE). During 2002-2008, federal immigration personnel used haloperidol to sedate 356 deportees. By 2008, following court challenges over the practice, it was given to only three detainees. Following lawsuits, U.S. officials changed the procedure so the drug is administered only by the recommendation of medical personnel and under court order.[78][79]

Brand names

Haloperidol is sold under the tradenames Aloperidin, Bioperidolo, Brotopon, Dozic, Duraperidol (Germany), Einalon S, Eukystol, Haldol (common tradename in the US and UK), Halosten, Keselan, Linton, Peluces, Serenace and Sigaperidol.

Veterinary use

Haloperidol is also used on many different kinds of animals. It appears to be particularly successful when given to birds, e.g., a parrot that will otherwise continuously pluck its feathers out.[80]

References

  1. ^ Jump up to:a b c d e f g h i Kudo, S; Ishizaki T (December 1999). “Pharmacokinetics of haloperidol: an update”. Clinical pharmacokinetics 37 (6): 435-456. doi:10.2165/00003088-199937060-00001. PMID 10628896.
  2. Jump up^ “PRODUCT INFORMATION Serenace” (PDF). TGA eBusiness Services. Aspen Pharma Pty Ltd. 29 September 2011. Retrieved 29 May 2014.
  3. Jump up^ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. p. 229-230. ISBN 978-0-85711-084-8. edit
  4. ^ Jump up to:a b Brayfield, A, ed. (13 December 2013). “Haloperidol”. Martindale: The Complete Drug Reference. London, UK: Pharmaceutical Press. Retrieved 29 May 2014.
  5. Jump up^ “TGA Approved Terminology for Medicines” (PDF). Therapeutic Goods Administration. Australian Government, Department of Health and Ageing. July 1999. p. 66. Retrieved 29 May 2014.
  6. Jump up^ Rossi, S, ed. (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3. edit
  7. Jump up^ “WHO Model List of Essential Medicines” (PDF). World Health Organization. October 2013. p. 7, 35. Retrieved 22 April 2014.
  8. Jump up^ “Haldol Official FDA information, side effects and uses”. Drugs.com. Retrieved 2013-10-03.
  9. Jump up^ Giannini, A. James; Underwood, Ned A.; Condon, Maggie (2000). “Acute Ketamine Intoxication Treated by Haloperidol”. American Journal of Therapeutics 7 (6): 389–91.doi:10.1097/00045391-200007060-00008. PMID 11304647.
  10. Jump up^ Giannini, A. James; Eighan, Michael S.; Loiselle, Robert H.; Giannini, Matthew C. (1984). “Comparison of Haloperidol and Chlorpromazine in the Treatment of Phencyclidine Psychosis”. The Journal of Clinical Pharmacology 24 (4): 202–4.doi:10.1002/j.1552-4604.1984.tb01831.x. PMID 6725621.
  11. Jump up^ Cavanaugh, SV (1986). “Psychiatric emergencies”. The Medical clinics of North America 70 (5): 1185–202. PMID 3736271.
  12. Jump up^ Currier, Glenn W. (2003). “The Controversy over ‘Chemical Restraint’ In Acute Care Psychiatry”. Journal of Psychiatric Practice 9 (1): 59–70. doi:10.1097/00131746-200301000-00006. PMID 15985915.
  13. Jump up^ Irving, Claire B; Adams, Clive E; Lawrie, Stephen (2006). “Haloperidol versus placebo for schizophrenia”. In Irving, Claire B. Cochrane Database of Systematic Reviews (4): CD003082. doi:10.1002/14651858.CD003082.pub2. PMID 17054159.
  14. Jump up^ Allen, MH; Currier, GW; Hughes, DH; Reyes-Harde, M; Docherty, JP; Expert Consensus Panel for Behavioral Emergencies (2001). “The Expert Consensus Guideline Series. Treatment of behavioral emergencies”. Postgraduate Medicine (Spec No): 1–88; quiz 89–90. PMID 11500996.
  15. Jump up^ Allen, Michael H.; Currier, Glenn W.; Hughes, Douglas H.; Docherty, John P.; Carpenter, Daniel; Ross, Ruth (2003). “Treatment of Behavioral Emergencies: A Summary of the Expert Consensus Guidelines”. Journal of Psychiatric Practice 9 (1): 16–38. doi:10.1097/00131746-200301000-00004. PMID 15985913.
  16. Jump up^ Allen, Michael H.; Currier, Glenn W.; Carpenter, Daniel; Ross, Ruth W.; Docherty, John P. (2005). “Introduction: Methods, Commentary, and Summary”. Journal of Psychiatric Practice 11: 5. doi:10.1097/00131746-200511001-00002.
  17. Jump up^ Ballard, Clive; Lana, Marisa Margallo; Theodoulou, Megan; Douglas, Simon; McShane, Rupert; Jacoby, Robin; Kossakowski, Katja; Yu, Ly-Mee; Juszczak, Edmund; on behalf of the Investigators DART AD (2008). “A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)”. In Brayne, Carol. PLoS Medicine 5 (4): e76. doi:10.1371/journal.pmed.0050076.PMC 2276521. PMID 18384230. Lay summary – BBC News (April 1, 2008). “Neuroleptics provided no benefit for patients with mild behavioural problems, but were associated with a marked deterioration in verbal skills”
  18. ^ Jump up to:a b c d e “Haldol Official FDA information, side effects and uses”. Drugs.com. Retrieved 2013-10-03.
  19. Jump up^ “Haloperidol at Chemeurope”.
  20. ^ Jump up to:a b Work Group on Schizophrenia. “Practice Guideline for the Treatment of Patients With Schizophrenia Second Edition”. Retrieved 21 April 2014.
  21. Jump up^ Oosthuizen, P.; Emsley, R. A.; Turner, J.; Keyter, N. (2001). “Determining the optimal dose of haloperidol in first-episode psychosis”. Journal of Psychopharmacology 15 (4): 251–5. doi:10.1177/026988110101500403. PMID 11769818.
  22. Jump up^ Tauscher, Johannes; Kapur, Shitij (2001). “Choosing the Right Dose of Antipsychotics in Schizophrenia”. CNS Drugs 15 (9): 671–8. doi:10.2165/00023210-200115090-00001.PMID 11580306.
  23. Jump up^ Goodman and Gilman’s Pharmacological Basis of Therapeutics, 10th edition (McGraw-Hill, 2001).[page needed]
  24. Jump up^ American Academy of Hospice and Palliative Medicine. “Five Things Physicians and Patients Should Question”. Choosing Wisely: an initiative of the ABIM Foundation(American Academy of Hospice and Palliative Medicine). Retrieved August 1, 2013., which cites
    • Smith, Thomas J.; Ritter, Joseph K.; Poklis, Justin L.; Fletcher, Devon; Coyne, Patrick J.; Dodson, Patricia; Parker, Gwendolyn (2012). “ABH Gel is Not Absorbed from the Skin of Normal Volunteers”. Journal of Pain and Symptom Management 43(5): 961–6. doi:10.1016/j.jpainsymman.2011.05.017. PMID 22560361.
    • Weschules, Douglas J. (2005). “Tolerability of the Compound ABHR in Hospice Patients”. Journal of Palliative Medicine 8 (6): 1135–43.doi:10.1089/jpm.2005.8.1135. PMID 16351526.
  25. Jump up^ PRODUCT INFORMATION [Internet]. 2011 [cited 2013 Sep 29]. Available from:https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2011-PI-03532-3
  26. Jump up^ HALDOL® Injection FOR INTRAMUSCULAR INJECTION ONLY PRODUCT INFORMATION [Internet]. Janssen; 2011 [cited 2013 Sep 29]. Available from:https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2009-PI-00998-3
  27. Jump up^ Truven Health Analytics, Inc. DrugPoint® System (Internet) [cited 2013 Sep 29]. Greenwood Village, CO: Thomsen Healthcare; 2013.
  28. Jump up^ Joint Formulary Committee. British National Formulary (BNF) 65. Pharmaceutical Pr; 2013.
  29. ^ Jump up to:a b Leucht, Stefan; Cipriani, Andrea; Spineli, Loukia; Mavridis, Dimitris; Örey, Deniz; Richter, Franziska; Samara, Myrto; Barbui, Corrado; Engel, Rolf R; Geddes, John R; Kissling, Werner; Stapf, Marko Paul; Lässig, Bettina; Salanti, Georgia; Davis, John M (2013). “Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: A multiple-treatments meta-analysis”. The Lancet 382 (9896): 951–62.doi:10.1016/S0140-6736(13)60733-3. PMID 23810019.
  30. ^ Jump up to:a b Silvestri, Simone; Seeman, Mary V.; Negrete, Juan-Carlos; Houle, Sylvain; Shammi, C.M.; Remington, Garry J.; Kapur, Shitij; Zipursky, Robert B.; Wilson, Alan A.; Christensen, Bruce K.; Seeman, Philip (2000). “Increased dopamine D 2 receptor binding after long-term treatment with antipsychotics in humans: A clinical PET study”.Psychopharmacology 152 (2): 174–80. doi:10.1007/s002130000532.PMID 11057521.
  31. Jump up^ Dorph-Petersen, Karl-Anton; Pierri, Joseph N; Perel, James M; Sun, Zhuoxin; Sampson, Allan R; Lewis, David A (2005). “The Influence of Chronic Exposure to Antipsychotic Medications on Brain Size before and after Tissue Fixation: A Comparison of Haloperidol and Olanzapine in Macaque Monkeys”. Neuropsychopharmacology 30 (9): 1649–61. doi:10.1038/sj.npp.1300710. PMID 15756305.
  32. Jump up^ Konopaske, Glenn T.; Dorph-Petersen, Karl-Anton; Sweet, Robert A.; Pierri, Joseph N.; Zhang, Wei; Sampson, Allan R.; Lewis, David A. (2008). “Effect of Chronic Antipsychotic Exposure on Astrocyte and Oligodendrocyte Numbers in Macaque Monkeys”. Biological Psychiatry 63 (8): 759–65.doi:10.1016/j.biopsych.2007.08.018. PMC 2386415. PMID 17945195.
  33. Jump up^ Vernon, Anthony C.; Natesan, Sridhar; Modo, Mike; Kapur, Shitij (2011). “Effect of Chronic Antipsychotic Treatment on Brain Structure: A Serial Magnetic Resonance Imaging Study with Ex Vivo and Postmortem Confirmation”. Biological Psychiatry 69 (10): 936–44. doi:10.1016/j.biopsych.2010.11.010. PMID 21195390.
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External links

FDA approves Avastin to treat patients with aggressive and late-stage cervical cancer

August 15, 2014 10:05 am / Leave a comment


August 14, 2014

The U.S. Food and Drug Administration today approved a new use for Avastin (bevacizumab) to treat patients with persistent, recurrent or late-stage (metastatic) cervical cancer.

Cervical cancer grows in the tissues of the lower part of the uterus known as the cervix. It commonly occurs when human papillomaviruses (HPV), a virus that spreads through sexual contact, cause cells to become cancerous. Although there are two licensed vaccines available to prevent many types of HPV that can cause cervical cancer, the National Cancer Institute estimates that 12,360 American women will be diagnosed with cervical cancer and 4,020 will die from the disease in 2014.

Avastin works by interfering with the blood vessels that fuel the development of cancerous cells. The new indication for cervical cancer is approved for use in combination with chemotherapy drugs paclitaxel and cisplatin or in combination with paclitaxel and topotecan.

“Avastin is the first drug approved for patients with late-stage cervical cancer since the 2006 approval of topotecan with cisplatin,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It is also the first biologic agent approved for patients with late-stage cervical cancer and was approved in less than four months under the FDA’s priority review program, demonstrating the agency’s commitment to making promising therapies available to patients faster.”

The FDA reviewed Avastin for treatment of patients with cervical cancer under its priority review program because the drug demonstrated the potential to be a significant improvement in safety or effectiveness over available therapy in the treatment of a serious condition. Priority review provides an expedited review of a drug’s application.

The safety and effectiveness of Avastin for treatment of patients with cervical cancer was evaluated in a clinical study involving 452 participants with persistent, recurrent, or late-stage disease. Participants were randomly assigned to receive paclitaxel and cisplatin with or without Avastin or paclitaxel and topotecan with or without Avastin. Results showed an increase in overall survival to 16.8 months in participants who received chemotherapy in combination with Avastin as compared to 12.9 months for those receiving chemotherapy alone.

The most common side effects associated with use of Avastin in patients with cervical cancer include fatigue, decreased appetite, high blood pressure (hypertension), increased glucose in the blood (hyperglycemia), decreased magnesium in the blood (hypomagnesemia), urinary tract infection, headache and decreased weight. Perforations of the gastrointestinal tract and abnormal openings between the gastrointestinal tract and vagina (enterovaginal fistula) also were observed in Avastin-treated patients.

Avastin is marketed by South San Francisco, California-based Genentech, a member of the Roche Group.

Property Value Source
melting point 61 °C (FAB fragment), 71 °C (whole mAb) Vermeer, A.W.P. & Norde, W., Biophys. J. 78:394-404 (2000)

Db00112

Protein chemical formula C6538H10034N1716O2033S44
Protein average weight 149 kDa

A recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor (VEGF). Bevacizumab contains human framework regions and the complementarity-determining regions of a murine antibody that binds to VEGF. Bevacizumab is produced in a Chinese Hamster Ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicin and has a molecular weight of approximately 149 kilodaltons.

sequence

>"Bevacizumab light chain"
DIQMTQSPSSLSASVGDRVTITCSASQDISNYLNWYQQKPGKAPKVLIYFTSSLHSGVPS
RFSGSGSGTDFTLTISSLQPEDFATYYCQQYSTVPWTFGQGTKVEIKRTVAAPSVFIFPP
SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT
LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>"Bevacizumab heavy chain"
EVQLVESGGGLVQPGGSLRLSCAASGYTFTNYGMNWVRQAPGKGLEWVGWINTYTGEPTY
AADFKRRFTFSLDTSKSTAYLQMNSLRAEDTAVYYCAKYPHYYGSSHWYFDVWGQGTLVT
VSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVL
QSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEL
LGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREE
QYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPS
REEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDK
SRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK
Bevacizumab 
Monoclonal antibody
Type Whole antibody
Source Humanized (from mouse)
Target VEGF-A
Clinical data
Trade names Avastin
AHFS/Drugs.com monograph
Licence data EMA:Link, US FDA:link
Pregnancy cat. C (US)
Legal status ℞ Prescription only
Routes Intravenous
Pharmacokinetic data
Bioavailability 100% (IV only)
Half-life 20 days (range: 11–50 days)
Identifiers
CAS number 216974-75-3 Yes
ATC code L01XC07
DrugBank DB00112
UNII 2S9ZZM9Q9V Yes
KEGG D06409 Yes
ChEMBL CHEMBL1201583 
Chemical data
Formula C6638H10160N1720O2108S44 
Mol. mass approx. 149 kDa

Carbohydrate Metabolism

August 15, 2014 1:41 am / Leave a comment


larryhbern's avatarLeaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

Carbohydrate Metabolism

Larry H. Bernstein, MD, FCAP, Reporter and Curator

Leaders in Pharmaceutical Intelligence

http://pharmaceuticalintelligence.com/8-9-2014/Carbohydrate_Metabolism

This is the third portion of the discussion in a series of articles that began with signaling and signaling pathways. There are fine features on the functioning of enzymes and proteins, on sequential changes in a chain reaction, and on conformational changes that we shall return to.  These are critical to developing a more complete understanding of life processes.  I have indicated that many of the protein-protein interactions or protein-membrane interactions and associated regulatory features have been referred to previously, but the focus of the discussion or points made were different.  Even though I considered placing this after the discussion of proteins and how they play out their essential role, I needed to lay out the scope of metabolic reactions and pathways, and their complementary changes. These may not appear to be adaptive, if the…

View original post 6,261 more words

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