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Adis R&D Insight reports on drugs in research and development around
the world.
ADRD allows you to monitor stages of development of drugs from pre-
clinical through to market launch, with each drug being reviewed and
evaluated at every stage.
The information provided on each drug includes generic names and
synonyms, company names, development phases, development history, an
Adis evaluated rating of therapeutic value, a commercial summary by
stockbrokers Lehman Brothers, adverse events, pharmacology,
pharmacokinetics, pharmacodynamics, therapeutic trials and estimated
sales launch dates by country.
Evaluations are provided by licensed forecasts from the
stockbrokers, Lehman Brothers, and from Adis' own unique
therapeutic value rating of drugs.
ADRD will be of particular interest to those working in
pharmaceutical R&D, licensing and marketing, and researchers in
healthcare institutions.
Use ADRD to answer questions like:
- which products in phase III clinical trials are indicated for
Alzheimer's disease and have an Adis therapeutic value rating
of A or B?
- what new drugs are GSK currently developing?
- what renin inhibitors are in development in the USA?
- where and when is Glimepride expected to be launched and what are
the forecasted sales?
- which significant clinical trials have helped advance the
development of Remikiren?
Sources:
Data is collected from over 2,300 biomedical journals covering drugs
and therapeutics, news services, newsletters, company annual
reports, contact with companies, market intelligence, meetings and
conferences.
The database was first launched by Adis in 1995. Any drugs under
investigation at that time will continue to appear in the database.
Even if research is discontinued, or a drug has been successfully
launched, the record relating to the drug remains in the database.
AN - Accession number & update:
00014331 20031231.
TI - Title:
Bifeprunox.
SO - Source:
Adis R&D Insight.
SY - Synonyms:
Generic name: Bifeprunox
Synonyms: DU 127090
Chemical name: 1-(2-Oxo-benzoxazolin-7-yl)-4-(3-biphenyl)
methylpiperazinemesylate.
RN - CAS registry number:
350992-10-8.
IM - Image:
[[IMG SRC="14331"
MF - Molecular formula:
C24 H23 N3 O2.
CC - Therapeutic classes:
N4A (Anti-Parkinson Drugs), N5A (Antipsychotics).
AC - WHO ATC classes:
N04 (Anti-Parkinson Drugs), N05A (Antipsychotics).
ME - Mechanism of action:
Serotonin 1A receptor agonists, Serotonin 1 receptor agonists,
Serotonin receptor agonists, Neurotransmitter agonists,
Dopamine D2 receptor antagonists, Dopamine receptor
antagonists, Neurotransmitter antagonists.
CO - Company name:
Originator:
Solvay (Belgium), Solvay (USA).
Licensee(s):
Lundbeck A/S, Wyeth.
PA - Parent company:
Solvay.
PH - Drug development phases:
Phase Country Indication
----- ------- ----------
Phase III Europe Parkinson's disease.
Phase III Europe Schizophrenia.
Phase III USA Schizophrenia.
Phase II USA Parkinson's disease.
HP - Highest phase:
Phase III.
IN - Indications:
Parkinson's disease; Schizophrenia.
HI - Development history:
04-Dec-2001: Sales forecasts reviewed by Lehman Brothers
03-Jan-2001: Solvay and Lundbeck have entered into a
cooperative agreement for development of bifeprunox
15-Nov-2000: Preclinical studies have been added to the
adverse events and pharmacodynamics sections (847440,
847496, 847441)
31-Jul-2000: New profile.
EV - Evaluation:
Schizophrenia 77(PO).
CS - Commercial summary:
Psychosis, Parkinsons / D2 partial agonist/ant + 5-HT1A
agonist
-------------------------------------------------------------
Company Region Launch Date Peak Sales Expiry
-------------------------------------------------------------
Lundbeck Eur 2007 $500m
Solvay Pharmaceuticals Eur 2007 $500m
-------------------------------------------------------------
Schizophrenia, Bipolar disorder / D2 partial agonist/ant +
5-HT1A agonist
-------------------------------------------------------------
Company Region Launch Date Peak Sales Expiry
-------------------------------------------------------------
Solvay Pharmaceuticals US 2007 $1000m 2017
Wyeth US 2007 $1000m 2017
-------------------------------------------------------------
Copyright (C) Lehman Brothers International. All rights
reserved.
SU - Summary:
Pharmacodynamics:
Antipsychotic-like effects in animal models; demonstrates
partial agonism at dopamine D sub(2) receptors with partial
agonism at serotonin sub(1A) receptors; displays partial
agonist properties at serotonin sub(7A) receptors; shows
potent antagonism on cloned human dopamine D sub(2) receptors
expressed in CHO cells; induced a dose-related reversal of
MPTP-induced hypomobility and disability in marmosets; reduces
prolactin release in rats; reverses amfetamine-, ketamine- and
methylphenidate- induced behaviours in rats; exhibits weak
effects on catelepsy in rats
Mechanism of action:
Serotonin 1A receptor agonists
Serotonin 1 receptor agonists
Serotonin receptor agonists
Neurotransmitter agonists
Dopamine D2 receptor antagonists
Dopamine receptor antagonists
Neurotransmitter antagonists
Activity versus parent drug: unspecified parent
Route(s) of Administration: PO
Administration Freq.(per day):
Drug Interactions:
Unknown.
IN - Introduction:
Solvay Pharmaceuticals and H. Lundbeck are jointly developing
bifeprunox (DU 127090) for the treatment of the positive and
negative symptoms of schizophrenia. Bifeprunox is an atypical
antipsychotic agent that acts as a partical antagonist at
dopamine D sub(2) receptors, and has serotonin sub(1A)
agonist effects. However, in contrast to currently available
antipsychotics, bifeprunox is not associated with weight gain
or hyperprolactinaemia, and does not effect glucose of lipid
control. Phase III trials for the treatment of schizophrenia
and Parkinson's disease are underway.
(...)
AE - Adverse Events:
Animal toxicology: the ED sub(50) of bifeprunox for induction
of catalepsy in rats was > 25 mg/kg PO, compared with an ED
sub(50) of 6.7 mg/kg for haloperidol/3/.
Single doses of bifeprunox (0.125-50 mg/kg PO) had mild
sedative effects in Cebus monkeys that had been sensitised to
antipsychotic agents. It produced mild dystonia and
parkinsonian symptoms. In contrast to haloperidol, the
extrapyramidal-like side effects of bifeprunox plateaued at a
low dose and modestly decreased with higher doses/4/.
PC - Pharmacology:
Pharmacokinetics:
Pharmacodynamics (Parkinson's Disease and Movement
Disorders):
Bifeprunox showed potent but incomplete antagonism (pA2 =
10.1) at the D2 receptor with an intrinsic activity of 28%
compared with quinpirole on cloned human d2 receptors
expressed in CHO cells. It produced a minimal decrease in
dopamine levels in the nucleus accumbens of freely moving
rats.
(...)
TR - Therapeutic trials:
Psychotic Disorders:
Results from a placebo-controlled, phase II trial of
bifeprunox showed that the agent was both effective and
well tolerated in patients with schizophrenia. Extensive
phse III trials have been started as a result of the
positive results seen a phase II/13/.
CR - Cited references:
1. Solvay Pharmaceuticals. Solvay Pharmaceuticals and Wyeth
Pharmaceuticals Sign Agreements to Co-Develop and Co-
Commercialize CNS Compounds and Co-Promote EFFEXOR XR. Media
Release. : 1 Apr 2004. Available from: URL: http://www.
solvaypharmaceuticals-us.com. (English).
2. Lundbeck A/S, Solvay Pharmaceuticals. Bifeprunox enters
clinical phase III. Media release. : 2 Sep 2003. Available
from: URL: http://www.lundbeck.com. (English).
3. Van Vliet BJ, Mos J, et al. DU 127090: a highly potent,
atypical dopamine receptor ligand-a putative potent full
spectrum antipsychotic with low EPS potential. European
Neuropsychopharmacology. 10 (Suppl. 3): 293, Sep 2000.
(English).
(...)
ED - Major change date:
20050323.
OC - Occurrences:
AN (1).
Label / description Example
AN Accession number 1_: 00002010.AN.
update 2_: 20010125.AN.
TI Title 3_: NARATRIPTAN.TI.
SO Source - same for all documents -
SY Synonyms 4_: GR ADJ 85548.SY.
RN CAS registry number 5_: 121679-13-8.RN.
IM Image 6_: IMAGE=YES
-see also notes-
MF Molecular formula 7_: C17 ADJ H25 ADJ N3 ADJ
O2 ADJ S.MF.
CC EphMRA ATC classes 8_: N2C.CC.
# at 1, 2, 3 or 4 digits 9_: N#
or 10_: CC=N2C
or 11_: MIGRAINE.CC.
AC WHO ATC classes 12_: N02C#
or 13_: AC=N02C$
ME Mechanism of action 14_: AMYLIN ADJ AGONISTS.ME.
or 15_: ME=AMYLIN-AGONISTS
or for a list 16_: ..ROOT ME=SEROTONIN
CO Company name 17_: GLAXOSMITHKLINE.CO.
(superlabel for OR LC)
OR Originator 18_: DAINIPPON.OR.
LC Licensee 19_: RHONE-POULENC$.LC.
or 20_: RHONE ADJ POULENC.LC.
PA Parent company 21_: GLAXOSMITHKLINE.PA.
OT Other companies 22_: SCHWARZ-PHARMA.OT.
PH Phases 23_: LAUNCHED ADJ CANADA.PH.
HP Highest phase
or 24_: HP=LAUNCHED
..ROOT HP= for a list
IN Indications 25_: MIGRAINE.IN.
HI Development history 26_: TREATMENT WITH
MIGRAINE.HI.
EV Evaluation (on a scale from 27_: ANXIETY ADJ DISORDER$.EV.
020 (low) to 100 (high)) EV=058
CS Commercial summary 28_: US.CS.
SU Summary 29_: ADVERSE WITH NAUSEA.SU.
TX Text 30_: SALES WITH GROWTH.TX.
(superlabel for IT AE PC TR)
IT Introduction 31_: TRIALS WITH JAPAN.IT.
AE Adverse events 32_: DIZZINESS.AE.
PC Pharmacology 33_: PLASMA ADJ LEVEL.PC.
TR Therapeutic trials 34_: HEADACHE WITH RELIEF.TR.
CR Cited references 35_: HEADACHE WITH LANCET.CR.
XR Cross references 36_: 800634763.XR.
ED Major change date 37_: 20010123.ED.
OC Occurrences - display only -
Active metabolites 38_: AM=Y
Route of elimination 39_: EL=RENAL
..ROOT EL= for a list 40_: ..ROOT EL=
1_: MIGRAINE
ED Major change date YYYYMMDD 2_: ..L 1 ED=20010123
UDATE Update date YYYYMMDD 3_: ..L 1 UDATE>20001231
UMONTH Update month YYYYMM 4_: ..L 1 UMONTH<200102.
Images (IM) will display ONLY in the ALL/FULL format, and only when
searching via DataStar Web or DataStar Classic on the Web.
By paragraph - title, company name _: ..P TI, CO 1-10
SHORT AN TI SO SY CC AC CO (OR LC) PA HP IN ED
MEDIUM AN TI SO SY CC AC ME CO (OR LC) PA OT PH HP EV CS SU IT ED
LONG AN TI SO SY CC AC ME CO (OR LC) PA OT PH HP HI EV CS SU TX
(IT AE PC TR) ED
ALL AN TI SO SY RN IM MF CC AC ME CO (OR LC) PA OT PH HP HI EV
CS SU TX (IT AE PC TR) CR XR ED OC
HITS All paragraphs where your search terms occur
KWIC Context of your search terms from the TX paragraph
FREE AN TI SO ED OC
_: ..P MEDIUM 5,19-20
The EphMRA ATC Codes, WHO ATC Codes, Mechanisms of Action
and Indications can be obtained from the producer and are listed
in BASE, search BASE-ADRD.
Please note that WHO and EphMRA ATC codes are sometimes assigned
by ADIS. If no specific code exists, a code may be created
according to guidelines for the respective list. Codes are
reviewed annually for accuracy. ADIS may assign more than one
code for a drug for which the mechanism is not yet fully elucidated.
IM - Image
As of the January 2004 reload, documents in ADRD may contain images.
These images are only viewable via Web-based interfaces: DataStar
Web or DataStar Classic on the Web.
Additionally, note that the IM field is included in the ALL print
format only.
EV - Evaluation
The Adis evaluation provides a valid and reproducible rating
guide for the clinical potential of new agents undergoing research
and development. The system is based on the assignment of a
numerical score to up to 20 key evaluation criteria.
The ratings are derived from the literature available at the
time the evaluation is undertaken; the degree of certainty in
the Adis rating will therefore depend on the number of criteria
evaluated in the light of currently available information. Ratings
are updated as new information is published in the literature.
Ratings are specific to a particular indication and/or route of
administration (or dosage form). Thus, a drug may have multiple,
different ratings.
Criteria evaluated to generate an Adis Therapeutic Rating:
- Preclinical - Chemistry & Pharmacodynamics:
Chemical structure (noverlty), mechanism of action (novelty),
specificity of action, stability to inactivation, selectivity,
secondary pharmacological properties, toxicity in animal studies,
pharmocokinetic attributes.
- Clinical - Pharmacokinetics:
Bioavailability, linear kinetics, interindividual variability,
formation of active metobolites, effects of renal or hepatic
dysfunction.
- Clinical - Clinical efficacy & use:
Convenience of administration, dose administration frequency,
relative efficacy against indicated disease.
- Clinical - Safety:
Adverse effects, contraindications/precautions, drug
interaction potential.
- Clinical - Clinical outcome & pharmacoeconomic considerations:
Clinical outcome, direct/acquisition cost, potential economic
benefits (indirect cost savings).
The ratings are defined as:
80-100%
Potential major therapeutic advance in providing substantially
greater clinical advantages in comparison with existing therapies,
and/or no effective alternatives currently available.
60-79%
Provides important patient benefits in comparison with existing
therapies, e.g. greater effectiveness or safety (or both), or
has particular attributes that will potentially provide important
benefits.
45-59%
Provides equivalent efficacy and/or some/modest benefits in
comparison with existing therapies, e.g. greater patient
convenience, usefulness in particular populations, fewer
adverse effects or interactions.
0-44%
Little or no advantages in comparison with existing therapies.
Cross references to relevant documents in Adis' Clinical Trials
Insight database (ACTI/AC00/ACZZ & AC89) are given, to provide
you with further information from the international literature
on drugs.
Use the ..ROOT command with the quick code EV= to retrieve
documents relating to drugs which fall within a specified
evaluation score range. To retrieve an individual evaluation
score, use the EV= quick code together with a number between 001
and 100 (it is essential that you add leading zeroes to make the
number up to three digits in length when searching with the EV=
quick code), e.g.:
1_: EV=045
ED - Major change date
The major change date is the date when either the document was first
added to Adis' database, or when major changes were last made. A major
change is defined as significant editorial changes and/or the drug
changing phase.
Search Options:
..SET PLURALS ON and ..SET MEDWORD ON can be selected in ADRD.
..RANK and ..MAP: Are available in the RN and XR paragraphs.
Guides:
Guide to ADRD appears in Biomedical Manual and online in BASE -
search BASE-ADRD.
ADIS DATA INFORMATION BV
Database copyrighted by Adis Data Information BV. Data may not be
duplicated in hard copy or machine-readable format without
written permission of Adis Data Information BV.
If data is to be distributed under The Dialog Corporation's
Redistribution and Archiving (ERA) policy, distribution
is restricted to the company and geographical boundaries of the
country where the data was downloaded. Data which has been
downloaded under this provision may not be sold or resold to a third
party outside the company organization.
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