CURRICULUM VITAE - DR ROBERT WILLIAM GRISTWOOD
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`28. 09. 1952
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`British
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`Sebel House, 3 Owls Close, Whittlesford, Cambridge CB22 4PL UK.
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`Nobel Grammar School Stevenage, U.K. (1964-1970)
`North Hertfordshire College, U.K. (1970-1972)
`North East London Polytechnic, U.K. (1972-1976) BSc
`Smith Kline in collaboration with University of Oxford, U.K. (1978-1982)
`PhD
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`BSc (Applied Biology), PhD (Pharmacology)
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`Qualifications
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`Society Membership British Pharmacological Society
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`Biochemical Society
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`British Toxicology Society
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`Society of Medicines Research
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`Sociedad Espanola de Farmacologia
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`Editorial functions Editor of British Journal of Pharmacology 1992 - 1997
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`Editor of Journal of Cardiovascular Pharmacology 1987 - 1995
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`Editor of Expert Opinion on Investigational Drugs 1992 – 2006
`Editor of Current Opinion in Anti-inflammatory and Immunomodulatory
`Investigational Drugs 1997-2000
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`Employment
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`1974-1975. Pharmacological research in the department of Medicinal Biology, Pfizer
`Central Research, Sandwich, Kent, U. K. Spent 1 year on research which was in support
`of the PDE (phosphodiesterase) inhibitor cardiac stimulant programme and the development
`of the selective PDE inhibitor buquineran.
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`1976-1988. Cardiovascular/ respiratory pharmacological / biochemical research within
`Pharmacology department, Smith Kline Research Ltd. Welwyn, U.K. Final position was
`Associate Director of Pharmacology, Head of cardiovascular, respiratory and
`electrophysiology groups. Direct reporting staff, 3 PhDs, 6 graduates, 1 undergraduate and 1
`research fellow. Carried out a variety of cardiovascular, respiratory and electrophysiological
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`Date of birth:
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`Nationality:
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`Educated:
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`investigations, a number of which have been reported in the literature (see references). Initial
`work (including PhD thesis) was concerned with histamine receptors and possible additional
`clinical utilities of the H2 antagonist cimetidine. Was later leader of a major research
`programme concerned with the identification of novel agents for the treatment of congestive
`heart failure. This involved the coordination of biology and chemistry research within Smith
`Kline in both UK and USA. Two compounds, both selective PDE 3 inhibitors, were selected
`for development, SK&F 94120 and siguazodan (SK&F 94836). Subsequently initiated and
`led another major world-wide (Welwyn and Philadelphia) research programme concerned
`with PDE 5 inhibitors, this is believed to be the first such programme to be established.
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`1988-1993. Director of Biology R&D at Laboratorios Almirall, Barcelona, Spain. Almirall
`Prodesfarma is Spain’s leading national pharmaceutical company and currently has over
`2000 employees. Whilst there, established a number of new research programmes including
`selective PDE 4 inhibitors, potassium channel activators, CCK antagonists, flosequinan like
`cardiostimulants (PDE 3 inhibitors), 5HT agonists and antagonists as anxiolytic, anti emetic,
`gastric prokinetic and anti-migraine agents. Was directly involved in the developments of
`ebastine and its active metabolite carebastine both non-sedating anti histamines, pancopride
`a 5HT3 antagonist anti-emetic, LAS Z 019 a 5HT4 agonist, prokinetic agent, LAS 31025, a
`selective PDE4 inhibitor, which progressed to clinical phase 3 for asthma and chronic
`obstructive pulmonary disease, and almotriptan, an anti-migraine agent. This included the
`responsibility for pre-clinical biology studies, including toxicology, DMPK and external
`pharmacology/biochemistry which were conducted both internally and within contract
`research organizations and academic institutions world-wide.
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`1993-1996. Head of Biology R&D at Chiroscience Ltd., Cambridge, U. K. Reporting staff
`25 in Biochemistry and Pharmacology departments. As Head of Biology R&D, was
`responsible for the establishment of biological research and development within the
`company. This involved the recruitment of research staff and the setting up of the
`biochemistry and pharmacology laboratories. Was also responsible for Toxicology and
`DMPK. Initiated and was project leader for the selective PDE 4 inhibitor programme which
`was successfully out-licensed. Was project leader for the development of Chirocaine
`(levobupivacaine), a single enantiomer local anaesthetic, through to clinical proof of principle
`and represented Chiroscience at the presentation to the US FDA advisory committee in
`January 1999. Chirocaine, which is currently marketed in 20 plus Countries, was the first
`product from a UK biotech company to be approved in the USA.
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`1996-Present. Director of Cambridge BioConsultants Ltd., Cambridge U.K. Was founder
`of the company, which has provided consultancy to a number of clients. This includes
`advising on pharmacology, DMPK and toxicology studies, the writing of expert reports for
`drug registration, CTX submissions, Investigators Brochures for clinical studies,
`presentations to regulatory authorities (in UK and USA) and numerous due diligence studies
`conducted on behalf of venture capital organizations.
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`1998-2007. Director of Arachnova Ltd., Cambridge U. K. Was co-founder of the company
`in 1998. Arachnova Ltd. specialized in the identification of new therapeutic uses for existing
`drugs.
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`2000-2007. Director and CSO of Arachnova Therapeutics Ltd., St Helier Jersey. Was co-
`founder of the company in September 2000. Arachnova Therapeutics was a venture capital
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`backed pharmaceutical company, which specialized in the development and
`commercialization of projects largely identified by Arachnova Ltd. The company had a
`number of projects in the areas of atopic dermatitis, neuropathic pain, urinary incontinence,
`functional bowel disease, hypertrophic scarring, Dupuytren’s contracture and pulmonary
`fibrosis. The company effectively ceased once Its key projects, related to MCI225, were out-
`licensed to a 3rd party in 2006-2007.
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`2007-present CSO Acacia Pharma PLC., Cambridge UK. Was a co-founder of the
`company. Acacia Pharma is a venture capital backed pharmaceutical company focused on
`hospital-based supportive care and in particular cancer supportive care. Current clinical
`development projects are in the areas of post operative nausea and vomiting, chemotherapy
`induced nausea and vomiting, cancer cachexia and cancer related xerostomia.
`Responsibilities include project discovery, DMPK and toxicology.
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`Publications (full papers/ reviews)
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`1. Characterisation of an isolated working guinea-pig heart including effects of histamine and
`noradrenaline. Flynn S. B., Gristwood R. W. and Owen D. A. A. (1978). J. Pharmacol. Meth.,
`1, 183-195.
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`2. Differentiation of the roles of histamine H1-and H2- receptors in the mediation of the
`effects of histamine in the working heart of the guinea-pig. Flynn S. B., Gristwood R. W. and
`Owen D. A. A. (1979). Br. J. Pharmacol, 65, 127-137.
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`3. Cardiovascular studies with impromidine (SK&F 92676), a new, very potent and specific
`histamine H2- receptor agonist. Owen D. A. A., Harvey C. A. and Gristwood R. W. (1979). J.
`Pharm. Pharmacol., 31, 577-582.
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`4. Effects of histamine on human isolated heart muscle. Comparison with effects of
`noradrenaline. Gristwood R. W., Lincoln J. C. R. and Owen D. A. A. (1981). Br. J.
`Pharmacol., 32, 145-146.
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`5. Histamine release from human right atrium. Gristwood R. W., Lincoln J. C. R., Owen D. A.
`A. and Smith I. R. (1981). Br J. Pharmacol., 74, 7-9.
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`6. Response of human ventricular heart muscle to histamine. Gristwood R. W., Owen D. A.
`A., Eckel L., Satter P. and Nawrath H. (1981). J. Pharm. Pharmacol., 33, 246-247.
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`7. Inotropic and electrophysiological effects of histamine on human ventricular heart muscle.
`Eckel L., Gristwood R. W., Nawrath H., Owen D. A. A. and Satter P. (1982). J. Physiol., 330,
`111-123.
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`8. Evidence that oxmetidine inhibits transmembrane calcium flux in cardiac and vascular
`tissue. Gristwood R. W., Jim K. F., Macia R. W., Matthews W. D., Morl C. J. and Owen D. A.
`A. (1985). Br. J. Pharmacol., 85, 923-932.
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`9. Some studies on the release of histamine from mast cells treated with D- tubocurarine. Ali
`H., Gristwood R. W. and Pearce F. L. (1986). Agents and Actions, 18, 71-73.
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`10. Pharmacological studies with SK&F 94120 a novel positive inotropic agent with
`vasodilator activity. Gristwood R. W., Eden R. J., Owen D. A. A. and Taylor E. M. (1986). J.
`Pharm. Pharmacol., 89, 335-340.
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`11. Impromidine is a partial agonist on human ventricular myocardium. English T. A. H.,
`Gristwood R. W., Owen D. A. A. and Wallwork J. (1986). Br. J. Pharmacol., 89, 335-340.
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`12. Analysis of cardiac responses to a selective phosphodiesterase III inhibitor, SK&F
`94120, on isolated myocardium including human ventricular myocardium from "end stage"
`failure patients. Gristwood R. W., English T. A. H., Wallwork J., Sampford K. A. and Owen D.
`A. A. (1987). J. Cardiovasc. Pharmacol., 9, 719-727.
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`13. The "ex vivo" effects of thyroid status on atrial and ventricular electrophysiology in rats.
`Rothaul A. L. and Gristwood R. W. (1988). Can. J. Phys. Pharmacol, 66, 90-94.
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`14. "In vivo" pharmacology studies with SK&F 94836, a potent inotrope/ vasodilator with a
`sustained duration of action. Gristwood R. W., Comer M. B., Eden R. J., Taylor E. M., Turner
`J. A., Wallduck M. and Owen D. A. A. (1988). Br. J. Pharmacol., 93, 893-901.
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`15. Effects of theophylline compared with prednisolone on late phase airway leukocyte
`infiltration in guinea-pigs. Gristwood R. W., Llupia J., Fernandez A. G. and Berga P. (1991).
`Int. Arch. Allergy Appl. Immunol., 94, 293-294.
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`16. Effects of prednisolone, salbutamol and theophylline on bronchial hyperreactivity and
`leukocyte chemokinesis in guinea-pigs. Llupia J., Fernandez A. G., Llenas J. and Gristwood
`R. W. (1991). Drugs Exp. Clin. Res., 17(8), 395-398.
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`17. Studies on the cardiac actions of flosequinan in vitro. Gristwood R. W., Beleta, J., Bou J.,
`Cardelus I., Fernandez A. G., Llenas J. and Berga P. (1992). Br. J. Pharmacol., 105,
`985-991.
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`18. The calcium channel blocker LAS 30538, unlike nifedipine, verapamil, diltiazem or
`flunarizine, potently inhibits insulin secretion in rats and dogs. Gristwood R. W., Furman B.
`L., Llenas J., Jauregui J. and Berga P. (1992). J. Pharm. Pharmacol., 44, 851-855.
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`19. Cardiovascular effects of LAS 30538, a new vascular selective calcium channel blocker.
`Cardelus I., Bou J., Llenas J., Berga P. and Gristwood R. W. (1992). J. Pharm. Pharmacol.,
`44. 830-835.
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`20. Pancopride, a potent and long-acting 5HT3 receptor antagonist, is orally effective against
`anticancer drug-evoked emesis. Fernandez A. G., Puig J., Beleta J., Domenech T., Bou J.,
`Berga P., Gristwood R. W. and Roberts D. J. (1992). Eur. J. Pharmacol., 222, 257-264.
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`21. Investigations into the role of PDE IV in bronchorelaxation including studies with human
`bronchus. Cortijo J., Bou J., Beleta J., Cardelus I., Llenas J., Morcillo E. and Gristwood R. W.
`(1993). Br. J. Pharmacol. 108, 562-568.
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`22. Effectos cardiovasculares de los inhibidores de la fosfodiesterasa. Gristwood R. W.
`(1993). Excerpta Medica, Investigacion en hipertension, 74-80.
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`23. Identification and characterization of serotonin 5HT4 receptor binding sites in human
`brain: comparison with other mammalian species. Domenech T., Beleta J., Fernandez A. G./
`Gristwood R. W., Cruz-Sanchez F., Tolsa E. and Palacios J. M. (1994). Mol. Brain Res., 21,
`176-180.
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`24. Mecamylamine reverses physostigmine- induced attenuation of scopolamine- induced
`hyperactivity. O' Neill M. F., Fernandez A. G., Gristwood R. W. and Palacios J. M. (1994). J.
`Neural Transm [Gen Sect], 96, 9-18.
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`25. Meeting of the British Pharmacological Society 5-7th January 1994, London U. K.
`Gristwood R. W. (1994). Exp. Opin. Invest. Drugs 3 (4): 397-398.
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`26. Pharmacokinetic studies of pancopride in rat and dog. Martinez-Tobed A., Aubets J.,
`Anton M. J. and Gristwood R. W. (1994). Eur. J. Drug Metab. and Pharmacokinetics, Special
`Issue participants papers of Proceedings of 5th European Congress of Biopharmaceutics
`and Pharmacokinetics held in Brussels April 1993.
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`27. Reduced cardiotoxicity of levobupivacaine compared with racemic bupivacaine
`(Marcaine): new clinical evidence. Gristwood R. W., Bardsley H., Baker, H. and Dickens J.
`(1994). Exp. Opin. Invest. Drugs, 3(11), 1209-1212.
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`28. Pharmacology and toxicological profile of LAS 30538: a new vascular selective calcium
`channel blocker. Llenas J., Cardelus I., Bou J., Gras J., Jauregui J. Martinez-Tobed A. and
`Gristwood R. W. (1995). Cardiovascular Drug Reviews, 13 (1) 1-18.
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`29. Phosphodiesterase (PDE) 4 inhibitors: anti inflammatory drugs of the future? Teixeira M.,
`Gristwood R. W., Cooper N. and Hellewell P. G. (1997). Trends in Pharmacol Sci., 18,
`164-168.
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`30.The local anaesthetic potency of levobupivacaine does not differ from racemic
`bupivacaine (Marcain): first clinical evidence. Bardsley H, Gristwood R. W., Watson N. and
`Nimmo W. (1997). Exp. Opin. Invest. Drugs, 3, 1209-1212.
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`31. A comparison of the inhibitory activity of selective PDE4 inhibitors on eosinophil
`recruitment in guinea pig skin. Teixeira M. M., Miotla J. M., Cooper N., Gristwood R. W. and
`Hellewell P. G. (1997). Mem. Inst. Oswaldo Cruz, 92 Suppl 2, 193-196.
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`32. A comparison of the cardiovascular effects of levobupivacaine and racemic bupivacaine
`following intravenous administration to healthy volunteers. Bardsley H, Gristwood R. W.,
`Baker H., Watson N. and Nimmo W. (1998). Brit. J. Clin. Pharmacol., 46, 1863-1871.
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`33. Cardiotoxicity of histamine and the possible role of histamine in the arrhythmogenesis
`produced by certain antihistamines. Llenas J., Cardelus I., Heredia A., de Mora F. and
`Gristwood R. W. (1999). Drug Saf. 21 Suppl, 33-38.
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`34. A comparison of the inhibitory activity of PDE4 inhibitors on leucocyte PDE4 activity in
`vitro and eosinophil trafficking in vivo. Cooper N., Teixeira M. M., Warneck J., Wills R. E.,
`Macari D. M., Gristwood R. W. and Helliwell P. G. (1999). Br. J. Pharmacol. 126, 1863-1871.
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`35. Levobupivacaine: a new long acting local anaesthetic agent. Gristwood R. W. and
`Greaves J. L. (1999). Exp. Opin. Invest. Drugs. 8, 861-876.
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`36. Pharmacological profile of LAS 31180, a new inotropic/vasodilator quinolone derivative.
`Gras J., Cardelus I., Beleta J., Gristwood R. W. and Palacios J. M. (2000).
`Arzneimittelforschung 50 (11) 980-986.
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`37. Cardiac and CNS Toxicity of Levobupivacaine. Strength of evidence for advantage over
`bupivacaine. Gristwood R. W. (2002). Drug Saf. 25 (3), 153-163.
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`ABSTRACTS:
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`1. Histamine induced increases in cardiac work in vitro. Flynn S. B., Gristwood R. W. and Owen
`D. A. A. (1977). Agents and Actions 8, 388P.
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`2. An isolated guinea-pig working heart. Preliminary studies with histamine and noradrenaline.
`Flynn S. B., Gristwood R. W. and Owen D. A. A. (1977). Br J. Pharmacol, 591, 530P.
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`3. The effects of histamine on the working kitten heart in vitro. Comparison with the effects of
`noradrenaline. Flynn S. B., Gristwood R. W. and Owen D. A. A. (1979). J. Physiol., 289, 65-66P.
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`4. Inhibition by cimetidine of cardiac stimulation due to mast cell degranulation. Gristwood R. W.,
`Owen D. A. A. and Smith I. R. (1980). Br. J. Pharmacol., 70, 105-106P.
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`5. Effects of histamine on human isolated heart muscle: comparison with effects of
`noradrenaline. Gristwood R. W., Lincoln J. R and Owen D. A. A. (1980). World Congress of
`Paediatric Cardiology, London, Abstract 361.
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`6. The mechanical and electrophysiological effects of histamine on human isolated ventricle.
`Gristwood R. W. and Nawrath H. (1980). Presented to European Working Group on Cardiac
`Electrophysiology, Berne.
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`7. Electropharmacological study of human ventricular heart muscle. Nawrath H. Eckel L.
`Gristwood R. W. and Zong X. (1981). IUPHAR 8th International Congress of Pharmacology,
`Japan, abstract 930.
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`8. The effects of ibopamine, an orally active dopamine analogue, on the guinea-pig isolated
`working heart. Gristwood R. W. and Owen D. A. (1983). Br. J. Pharmacol., 78, 30P.
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`9. Dog myocardium is very insensitive to histamine in vitro. Gristwood R. W. and Owen D. A. A.
`(1983). Presentation to 12th meeting European Histamine Research Society. Brighton.
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`10. Positive inotropic action of impromidine on human isolated ventricular myocardium. Cameron
`D., English T. A. H., Gristwood R. W., Owen D. A. A. and Wallwork J. (1984). IUPHAR 9th
`International Congress of Pharmacology, abstract 90.
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`11. SK&F 94120, a selective PDE III inhibitor, potentiates isoprenaline inotropic but not
`chronotropic responses in the guinea-pig heart. Blakemore R. C., Gristwood R. W., Owen D. A.
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`A. and Parsons M. E. (1985). Br J. Pharmacol., 86, 830P.
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`12. Specific inhibition of type III phosphodiesterase activity, comparison with positive inotropic
`potency. England P. J., Gristwood R. W., Leigh B. K., Owen D. A. A. and Reeves M. L. (1985).
`Br J. Pharmacol. 86, 630P.
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`13. Phosphodiesterase in the guinea-pig cardiac ventricle. Specific inhibition of type III activity by
`SK&F 94120. Gristwood R. W., Owen D. A. A. and ReevesM. L. (1985). Br J. Pharmacol. 85,
`224P.
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`14. Positive inotropic actions of SK&F 94120 on human isolated ventricular myocardium.
`Cameron D., English T. A. H., Gristwood R. W., Morl C. J., Owen D. A. A. and Wallwork J.
`(1985). Br. J. Pharmacol., 85, 226P.
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`15. SK&F 94120, a novel agent with positive inotropic and vasodilator activity. Coates W. J.,
`Eden R. J., Emmett, J. C. Gristwood R. W., Owen D. A. A., Slater R. A., Taylor E. M. and
`Warrington B. H. (1985). Br J. Pharmacol., 84, 22P.
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`16. The cardiac electrophysiological effects of methimazole pre-treatment in the rat. Flynn S. B.,
`Gristwood R. W., Owen D. A. A. and Rothaul A. L. (1985). Br. J. Pharmacol., 86, 422P.
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`17. Electrophysiological and mechanical actions of SK&F 94120, a selective PDE III inhibitor, on
`human ventricle in vitro. Gristwood R. W. and Owen D. A. A. (1985). Presented to European
`Working Group on Cardiac Electrophysiology, Freiburg.
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`18. The ex vivo electrophysiological effects of hypothyroidism and hyperthyroidism in rats.
`Gristwood R. W. and Rothaul A. L. (1985). Presented to European Working Group on Cardiac
`Electrophysiology Meeting, Freiburg.
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`19. Effects of dopamine on human ventricle in vitro, comparison with effects of isoprenaline,
`epinine and ibopamine. English T. A. H., Gristwood R. W., Owen D. A. A. and Wallwork J.
`(1985). Br. J. Pharmacol., 87, 203P.
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`20. SK&F 94120, an inotrope-vasodilator, inhibits aggregation and secretion of human platelets.
`Gristwood R. W., Rink T. J. and Simpson A. W. M. (1985). Br. J. Pharmacol., 87 11P.
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`21. SK&F 94120 and milrinone, unlike non-selective methylxanthine PDE inhibitors, does not
`inhibit myocardial A1- adenosine responses. Bath G., Gristwood R. W., Owen D. A. A. and
`Sampford K. (1985). Br. J. Pharmacol., 87, 181P.
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`22. Effects of rolipram on guinea-pig ventricles in vitro. Evidence of an unexpected synergism
`with SK&F 94120. Gristwood R. W. and Owen D. A. A. (1986). Br. J. Pharmacol., 87, 91P.
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`23. The electrophysiological effects of SK&F 94120, a selective PDE III inhibitor, on sheep
`purkinje fibres. Gristwood R. W., Owen D. A. A. and Rothaul A. L. (1986). Br. J. Pharmacol., 88,
`419P.
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`24. Are alpha-adrenoceptors coupled to contraction in human heart? Gristwood R. W., Ginsburg
`R. and Zera P. (1986). Presented at American Heart Association Meeting Dallas, November.
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`25. Evidence that it is the elevation of cAMP in a PDE III sensitive pool that results in inhibition of
`platelet excitatory responses. Gristwood R. W., Rink T. J. and Simpson A. W. M. (1986). Br. J.
`Pharmacol., 89, 571P.
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`26. The effect of SK&F 94120, rolipram and M&B 22948 on force of contraction and cyclic
`nucleotide content of cat myocardium. Gristwood R. W., Sampford K. A. and Williams T. J.
`(1986). Br J. Pharmacol., 89, 573P.
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`27. The ex vivo effects of hypo and hyperthyroidism in rats. Gristwood R. W. and Rothaul A. L.
`(1986). Presented to European Working Group on Cardiac Electrophysiology Meeting, Berne.
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`28. SK&F 94836, a potent orally active inodilator with a sustained duration of action in vivo.
`Gristwood R. W., Eden R. J., Owen D. A. A., Coates W. J., Emmett J. C., Slater R. A. and
`Warrington B. H. (1987). Presented to IUPHAR 10th International Congress of Pharmacology,
`Sydney.
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`29. The effects of epinine on human cardiac action potential characteristics. Gristwood R. W.
`and Rothaul A. L. (1987). Br J. Pharmacol., 91, 389P.
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`30. A comparison between the vasodilator and inotropic effects of amrinone, milrinone and
`SK&F 94836 in vitro. Wood L. M., Romanec R., Sampford K. A. and Gristwood R. W. (1987).
`Cardiovasc Drugs and Therapy, 1 (3) 303P.
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`31. Inhibition of histamine induced bronchoconstriction by SK&F 94836, salbutamol and
`theophylline in the anaesthetised guinea-pig. Gristwood R. W. and Sampford K. A. (1987). Br. J.
`Pharmacol., 92, 631P.
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`32. SK&F 94836- a potent inotropic agent is a selective inhibitor of type III PDE activity from
`several tissues. Reeves M. L., Gristwood R. W., Leigh B. K. and England P. J. (1987). Br. J.
`Pharmacol., 92, 773P.
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`33. Effects of PDE III inhibition on normal and mildly ischaemic sheep purkinje tissue. Gristwood
`R. W., Rothaul A. L., Frampton J. E. and McCall E. (1987). Presented to European Working
`Group on Cardiac Electrophysiology, Amsterdam.
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`34. SK&F 94836- a novel inodilator retains its activity in the presence of pharmacological doses
`of digoxin and captopril. Comer M. B., Gristwood R. W. and Wood L. M. (1987). Br J.
`Pharmacol., 92, 745P.
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`35. Effects of U44619 on mildly ischaemic myocardial tissue in vitro. Gristwood R. W., Rothaul
`A. L. and Frampton J. E. (1988). Br. J. Pharmacol., 93, 62P.
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`36.The antifibrillatory action of SK&F 94836. Gristwood R. W., Rothaul A. L. and Wood L. M.
`(1988). Br. J. Pharmacol., 93, 63P.
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`37. Effects of dopamine on human cardiac action potential characteristics. Gristwood R. W.,
`Rothaul A. L. and Frampton J. E. (1988). Br. J. Pharmacol. 95, 644P.
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`38. 4-Diphenylmethylamino-piperidine derivitives as potential calcium antagonists III. Pujol F.,
`Prieto J., Vega A., Moragues J., Llenas J., Berga P. and Gristwood R. W. (1989). Presented to
`VIth Congreso Internacional de la Sociedad Espanola de Quimica Terapeutica, Granada.
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`39. Receptores de serotonina: objectivo en la investigacion de nuevos productos farmacos
`selectivos. Berga P., Fernandez A. G., Llenas J. and Gristwood R. W. (1989). Presented to VI
`Congreso Internacional de la Sociedad Espanola de Quimica Terapeutica, Granada.
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`40. 4-Diphenylmethylamino-piperidine derivitives as potential calcium antagonists IV. Prieto J.,
`Pujol., Vega A., Moragues J., Llenas J., Berga P. and Gristwood R. W. (1989). Presented to VI
`Congreso Internacional de la Sociedad Espanola de Quimica Terapeutica, Granada.
`
`41. Posible implicacion de los canales de K+ en el efecto protector de pinacidil sobre la muerte
`inducida por BaCl2 en el raton. Llenas J., Cardelus I., Gristwood R. W. and Berga P. (1989).
`Rev. Pharmacol. Clin. Exp., 6, 239.
`
`42. Flosequinan (BTS 49465) behaves as an inhibitor of phosphodiesterase type III. Gristwood
`R. W., Llenas J., Puig C. and Berga P. (1990). Br. J. Pharmacol. 99, 18P.
`
`43. Bronchodilator effects of flosequinan. Comparison with the PDE III inodilator SK&F 94120.
`Llenas J., Cardelus I., Bou J., Gristwood R. W. and Berga P. (1990). Xith International Congress
`of Pharmacology, Amsterdam, abstract Fr-007.
`
`44. Comparison between the pharmacological respiratory profile of denbufylline and
`theophylline. Bou J., Beleta J., Cardelus I., Fernandez A. G., Llenas J., Llupia J., Berga P. and
`Gristwood R. W. (1990). Symposium on New Drugs for Asthma. XIth IUPHAR, Davos, abstract
`1/153/21.
`
`45. Cinitapride induced contractions and ACH release in resting guinea-pig myenteric plexus
`longitudinal muscle preparation are mediated by activation of 5HT4 receptors. Fernandez A. G.,
`Puig J., Bou J., Gristwood R. W. and Berga P. (1990). J. Gastroint. Mot. 2, (2) 141.
`
`46. Pancopride: a novel 5 HT3 antagonist with potent antiemetic action. Fernandez A. G., Puig
`J., Bou J., Gristwood R. W. and Berga P. (1990) Eur. J. Pharmacol. 183 (4) 1214.
`
`47. Effects of cinitapride in the isolated rat esophagus and dog L. E. S. pressure in vivo. Puig J.
`Fernandez A. G., Berga P. and Gristwood R. W. (1990). Gastroenterology 99, (4) 1211.
`
`48. The inotropic potency of flosequinan is consistent with its PDE III inhibitory activity. Beleta J.,
`Berga P., Fernandez A. G., Llenas J. and Gristwood R. W. (1991). Br. J. Pharmacol., 102, 209P.
`
`49. Activadores potenciales de canales de potasio. 1. Derivados de cianoguanidina y tiurea.
`Prieto J., Pujol F., Moragues J., Fernandez D., Cardelus J., Llenas J., Berga P. and Gristwood
`R. W. (1991). VIIth international Congress of Therapeutic Chemistry, Jaca.
`
`50. Activadores potenciales de canales de potasio. 2. Derivados de benzotiodiacina 1.1.
`diazoxido. Pujol F., Prieto J., Vega A., Fernandez D., Cardelus I., Llenas J., Berga P. and
`Gristwood R. W. (1991). VIIth International Congress of Therapeutic Chemistry, Jaca.
`
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`51. LAS 30538, a novel non-dihydropyridine calcium channel blocker with potent effects on
`vascular smooth muscle. Bou J., Puig J., Cardelus I., Fernandez A. G., Llenas J., Roberts D. J.,
`Berga P. and Gristwood R. W. (1991). Ivth International Congress of Pharmaceutical Sciences,
`Barcelona.
`
`52. Effects of prednisolone, salbutamol and theophylline on bronchial hyperreactivity and
`leucocyte chemokinesis in guinea-pigs. Llupia J., Fernandez A. G., Berga P. and Gristwood R.
`W. (1991). Symposium on Inflammation, antirheumatics, analgesics, immunomodulators
`(INWIN), Geneva, Switzerland, April 1991.
`
`53. Comparative inotropic and vasodilator effects of flosequinan and SK&F 94120 in the
`anaesthetised dog. Bou J., Cardelus I., Gras J., Berga P., Gristwood R. W. and Llenas J. (1991).
`Presented at IV Reuniao Conjunta das Sociedades Portuguesa e Espanhola de Farmacologia,
`Lisboa, March.
`
`54. Cardiodepressive effects of pinacidil and cromakalim on the guinea-pig isolated working
`heart and its reversion by glibenclamide. Bou J., Cardelus I., Gras J., Berga P. and Gristwood R.
`W. (1991). Presented at IV Reunioa Conjunta das Sociedades Portuguesa e Espanhola de
`Farmacologia. Lisboa March.
`
`55. Inhibicion por pancoprida de los vomotos y la gastroparesia asociados a la administracion de
`citostaticos. Berga P., Fernandez A. G., Llupia J. and Gristwood R. W. (1991). Presented at III
`Congreso Nacional de Oncologia Medica, Palma de Mallorca, May.
`
`56. Is hindlimb scratching in rats a suitable model for in vivo screening of 5-HT1D agonist
`compounds? Gristwood R. W., Puig J., Domenech T., Beleta J., Fernandez A. G. and Palacios
`J. M. (1992). Behavioural Pharmacology, 3, (1), 91.
`
`57. Pancopride, a new 5-HT3 antagonist with potent anxiolytic properties in rodents and
`primates. Fernandez A. G., Kelly M. E., Salcedo C., Puig J., Domeney A. M., Berga P.,
`Gristwood R. W. and Costal B. (1992). Behavioural Pharmacol., 3, (1), 43.
`
`58. Terfenadine, but not ebastine increases the force of contraction of guinea-pig ventricular
`strips by an action on histamine receptors. Llenas J., Cardelus I. and Gristwood R. W. (1992).
`Farm. Clin. Exp., Sept, pp 290.
`
`59. Efecto de la S-CM-GTNH2, un nuevo ligando selectivo para receptores para 5-HT1D, en
`algunas preperaciones vasculares. Bou J., Puig J., Fernandez A. G., Gristwood R. W. and
`Palacios J. M. (1992). Farm. Clin. Exp. Sept pp 290.
`
`60. Are 5-HT4 in addition to 5-HT3 receptors involved in drug-indiced reversal of cisplatin effects
`on gastric emtying in the rat? Fernandez A. G., Puig J., Beleta J., Gristwood R. W. and Berga P.
`(1992). Presented at 6th European Symposium on gastrointestinal motility. Barcelona,
`November.
`
`61. Rolipram and denbufylline, two phosphodiesterase inhibitors, induce gastric cytoprotective
`effects in the rat. Puig J., Fernandez A. G., Beleta J. and Gristwood R. W. (1992). Farm. Clin.
`Exp., Sept, p 290.
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`62. Hyperglycemic effect of LAS 30538, a calcium channel blocking drug, involves inhibition of
`insulin secretion. Furman B. L., Jauregui J. and Gristwood R. W. (1992). Presented at British
`Diabetic Association: Med & Scient Section, Spring Meeting U. K. January.
`
`63. Efectos del losartan sobre las repuestas inducidas por la angiotensina II en ratas
`desmeduladas con y sin pretratamiento con furosemida. Llenas J., Cardelus J., Gras J. Mesa A.
`and Gristwood R. W. (1993). XVIIth Meeting of the Spanish Pharmacological Society, Valladolid.
`Published in Rev. Farmacol. Clin Exp. (Special Number p 211.).
`
`64. Derivados de 1-alquil-3-amino-4(1H)-quinolonas como agentes cardiotonicos y/o
`vasodilatadores potenciales. Puig C., Crespo M. I., Pujol F., Pages L, Cardelus I., Gras J.,
`Llenas J. and Gristwood R. W. (1993). Congress of the Spanish Society of Therapeutic
`Chemistry, Salamanca.
`
`65. Pharmacokinetic studies of pancopride in rat and dog. Martinez-Tobed A., Aubets J., Anton
`M. J. and Gristwood R. W. (1993). Presented at 5th European Congress of Biopharmaceutics
`and Pharmacokinetics, Brussels. April.
`
`66. Mecamylamine restores scopolamine-induced hyperreactivity attenuated by physostigmine.
`O'Neill M. F., Fernandez A. G., Gristwood R. W. and Palacios J. M. (1993). Presented at 16th
`Annual Meeting of the Canadian College of Neuropsycopharmacology, Montreal, May.
`
`67. Phosphodiesterase IV inhibitors reduce the leucocyte chemokinesis induced by leukotriene
`B4 in guinea-pigs. Llupia J., Llenas J. and Gristwood R. W. (1993). Presented at 5th
`Interscience World Conference on
`Inflammation, antirheumatics, analgesics and
`immunomodulators, Geneva, April.
`
`68. Interspecies differences in the biotransformation of the new inotropic agent LAS 31180.
`Salva M., Carrera F., Gristwood R. W. and Martinez-Tobed A. (1993). ISSX Proceedings vol 3,
`5th European ISSX Meeting Tours France, September 1993.
`
`69. Reduced cardiotoxicity of levobupivacaine compared with racemic bupivacaine following
`intravenous administration to healthy volunteers. Bardsley H., Gristwood R. W., Baker H.,
`Watson N. and Nimmo W. (1996). 11th World Congress of Anesthesiologists Sydney 14-20th
`April.
`
`70. LAS 31025, a new compound with selective phosphodiesterase IV inhibitory activity. Beleta
`J., Bou J., Miralpeix M., Domenech T., Berga P., Gristwood R. W. and Palacios J. M. (1996).
`Presented at Third International Conference on Cyclic Nucleotide Phosphodiesterases:- From
`Genes to Therapies. Glasgow, July.
`
`71. LAS 31025, a new antiasthmatic compound combining airway antiallergic and
`bronchodilatory properties. Bou J., Llupia J., Puig J., Salcedo C., Gras J., Beleta J., Fernandez
`A. G., Llenas J., Berga P., Gristwood R. W. and Palacios J. M. (1996). Presented at Third
`International Conference on Cyclic Nucleotide Phosphodiesterases:- From Genes to Therapies.
`Glasgow, July.
`
`72. Characterization of LAS 31025: a new selective PDE IV inhibitor for bronchial asthma. Bou
`J., Beleta J., Llupia J., Cardelus I., Miralpeix M., Puig J., Domenech T., Salcedo C., Gras J.,
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`Fernandez A. G., Llenas J., Berga P., Gristwood R. W. and Palacios J. M. (1996). Presented at
`Third International Conference on Cyclic Nucleotide Phosphodiesterases:- From Genes to
`Therapies. Glasgow, July.
`
`73. Comparison of the cardiotoxic effects of bupivacaine, levobupivacaine and ropivacaine. An
`in vitro study in guinea