A B S T R A C T This article focuses on the difference that place makes to methodological practice. It argues, following Sin, that the spatial contexts in which methods are carried out remain 'largely excluded from any theorization of the social construction of knowledge ' (2003: 306). Through viewing 'place' as both a social and a geographical entity (following Cresswell, 1996), this article argues that although the importance of social relationships in methodology is widely accepted (through, for example, processes of researcher reflexivity), the influence of the 'where of method' has received less attention. The article addresses this issue by arguing for the explicit consideration of the geographical dimension of place in methodology. It does so by introducing the notion of a polylogic approach to method. The polylogic approach moves away from the conventional configuration of method as a dialogue (e.g. between researcher and researched) and towards method explicitly including researcher, researched, and the geographic place of methodology.K E Y W O R D S : geography, methodology, place, polylogue, research A R T I C L E 589Positioning place: polylogic approaches to research methodology
Flesinoxan is a representative of a series of new heterobicyclicaryl-piperazine analogues. In an attempt to develop N-substituted phenylpiperazine derivatives with psychotropic activity, it was found that a few analogues possessed a remarkable strong blood pressure lowering activity without psychotropic effects. Since early pharmacological studies indicated that this antihypertensive activity was mediated by a novel central mechanism of action, the structure-activity relationship for this blood pressure lowering activity was further investigated. This program finally resulted in flesinoxan: a potent, orally active, and long-acting antihypertensive agent. Flesinoxan is the active (+)-enantiomer of the originally obtained racemate.
CHEMISTRYFlesinoxan, compound X in Fig. 1, can be prepared by a 12-step synthesis starting with catechol (I) as outlined in Fig. 1 (6). Flesinoxan hydrochloride, a white microcrystalline powder with a melting point of 184-1 85°C and a solubility of 1% in water, has a pK, value of 6.7.Its molecular weight is 45 1.9 (monohydrochloride) and 4 15.4 (free base). The lipophilicity (log P = 3.3) is favorable for a centrally acting drug (1 1). The unformulated flesinoxan hydrochloride can be stored for at least 2 years at room temperature in the dark, whereas a 1% aqueous solution kept at 5"C, shows no decomposition after 30 days.
PHARMACOLOGY
Blood Pressure Lowering Activity
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