David T. Manallack

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The origins and operation of artificial neural networks are briefly described and their early application to data modelling in drug design is reviewed. Four problems in the use of neural networks in data modelling are discussed, namely overfitting, chance effects, overtraining and interpretation, and examples are given of the means by which the first three(More)
The regulation of the central sigma-binding site was investigated using both in vitro and in vivo manipulations in conjunction with radioligand binding. The displacement of the binding of R(+)-[3H]3-[3-hydroxyphenyl]-N-(1-propyl)piperidine [R(+)-[3H]3-PPP] to cortical homogenates by a range of drugs was consistent with the site labelled being a(More)
The effects of the subchronic administration of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine (MK-801) (0.5 mg/kg twice daily, 7 days) on N-methyl-D-aspartate, phencyclidine and sigma binding sites, behaviour and catecholamine turnover were investigated in the rat. Overt behaviours induced by MK-801 on day 7 were significantly altered(More)
The acid-base dissociation constant (pK(a)) of a drug is a key physicochemical parameter influencing many biopharmaceutical characteristics. While this has been well established, the overall proportion of non-ionizable and ionizable compounds for drug-like substances is not well known. Even less well known is the overall distribution of acid and base pK(a)(More)
Over 30 receptor-like kinases contain a guanylate cyclase (GC) catalytic centre embedded within the C-terminal region of their kinase domain in the model plant Arabidopsis. A number of the kinase GCs contain both functional kinase and GC activity in vitro and the natural ligands of these receptors stimulate increases in cGMP within isolated protoplasts. The(More)
Apicomplexan parasites, including Plasmodium falciparum and Toxoplasma gondii, the causative agents of severe malaria and toxoplasmosis, respectively, undergo several critical developmental transitions during their lifecycle. Most important for human pathogenesis is the asexual cycle, in which parasites undergo rounds of host cell invasion, replication, and(More)
Radioreceptor methods were used to quantitate the N-methyl-D-aspartate (NMDA) receptor-complex of ovine cerebral microvessels and cerebral gray matter. Specific binding of D[3H]2-amino-5-phosphono-pentanoate and [3H]1-[1-(2-thienyl)cyclohexyl]piperidine, ligands for the NMDA primary acceptor site and ionophore, respectively, was found in cerebral gray(More)
1. Phosphonate analogues of glutamate have been tested and compared as N-methyl-D-aspartate (NMDA) antagonists in electrophysiological and binding experiments. The compounds tested were three established NMDA antagonists: D-2-amino-5-phosphonopentanoate (D-AP5), DL-2-amino-7-phosphonoheptanoate (DL-AP7), 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate(More)
Computer-assisted molecular modelling techniques and electrostatic analyses of a wide range of phenycyclidine (PCP) and sigma ligands, in conjunction with radioreceptor studies, were used to determine the topographies of the PCP and sigma receptors. The PCP receptor model was defined using key molecules from the arylcyclohexylamine, benzomorphan, bridged(More)