By Edward L. Engelhardt (Eds.)
content material: [Beta]-adrenoceptor antagonists as antihypertensive brokers / Richard Clarkson --
Centrally appearing antihypertensive brokers / Wolfgang Hoefke --
Antihypertensives appearing through a peripheral mechanism / John E. Francis --
Antihypertensive brokers as obvious through the clinician / Gaddo Onesti.
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In the case of clonidine, pretreatment with 6 OHDA does not reduce the blood pressure lowering a c t i v i t y according to HAEUSLER and FINCH (34) and WARNKE and HOEFKE (35). This i s contrary to the r e s u l t s obtained by DOLLERY and REID (36) . Also a f t e r pretreatment with reserpine and blocking of noradrenaline synthesis with a-methyl-paratyrosine c l o n i d i n e retains i t s action on the sympathe t i c system (HAEUSLER (37)). The same holds true f o r the i n t e n s i f i c a t i o n of v a g a l l y mediated r e f l e x bradycardia by c l o n i d i n e (KOBINGER and PICHLER (38)).
The early work of the inventor, Jean Druey, at CIBA i n Basle, covered many variations of the structure and the structure-activity relationships established by Druey and his co-workers hold to this day (2, 3). Th most important compounds were those with the phthalazine (IV) and the pyridazine (V) ring systems. e 4 2 5 1 6 IV The following structure-activity relationships were defined: a) For prolonged hypotensive a c t i v i t y , the hydrazino group must be present i n the 1-position of phthalazine or the 3-position of pyridazine.
Explt. , (1974), 188, 394. , Clin. Explt. Pharmacol. , (1974), 1, 333. ; ACS Symposium Series; American Chemical Society: Washington, DC, 1976. 2 Centrally Acting Antihypertensive Agents WOLFGANG H O E F K E Department of Pharmacology, C. H. Boehringer Sohn, Ingelheim, W. Germany To show how comple p r e s s u r e w i t h t h e r a p e u t i c agents some i n f o r m a t i o n on the p h y s i o l o g y o f b l o o d p r e s s u r e r e g u l a t i o n is g i v e n ( F i g . 1 ) . The p r o c e s s o f r e g u l a t i n g b l o o d p r e s s u r e can be compared w i t h a p h y s i c a l c o n t r o l system where intravascular p r e s s u r e i s the c o n t r o l l e d p r o c e s s which has an o u t p u t v a r i a b l e c o n t i n u o u s l y measured by a feedback t r a n s d u c e r - the arterial baroreceptors providing aff e r e n t i n f o r m a t i o n f o r the controlling system in the c e n t r a l nervous system - i n s h o r t "the b l o o d p r e s s u r e r e g u l a t i n g system in the m e d u l l a o b l o n g a t a " .