Preliminary clinical pharmacological studies of S3341, a new hypotensive agent, and comparison with clonidine in normal males.
S3341, a new hypotensive agent which binds to alpha2-receptors in animal brain preparations, was studied in normal healthy male volunteers. A dose ranging study with 15 and 25 micrograms/kg of S3341 was performed in a double blind, placebo controlled randomised and balanced manner with 3 subjects. A decrease or BP without noticeable sedation (assessed by visual analogue scales) was seen. One, 2 mg of S3341, 0.1 and 0.2 mg of clonidine were then compared in a double blind, placebo controlled, randomised and balanced manner in 10 subjects. BP, heart rate, systolic time intervals (STI), critical flicker frequency, choice reaction time, pursuit rotor, stimulated salivary volume, and dryness of mouth and sedation with visual analogue scales, were measured at 0, 1.5, 3.0, 4.5 and 6.0 h after drug administration. The relationship between decreases in BP and sedation was assessed by linear regression analysis, with the former as the independent (predictor) response and the latter as the dependent (response) variate. Both drugs produced a similar decrease of BP which was significantly different from placebo. Changes in psychomotor function tests were not significant. Both drugs produced dryness of mouth and sedation which were significantly different from placebo but changes were less with S3341. Clonidine showed a significantly steeper slope than S3341 in the relationship between decreases in BP and sedation. This must be interpreted with caution as there was wide variation in the correlation between decreases in BP and sedation, but it may be possible to achieve lesser sedation with S3341.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006801:Humans; D008297:Male; D010080:Oxazoles / Q000494:pharmacology* / Q000633:toxicity; D000077769:Rilmenidine
D000316:Adrenergic alpha-Agonists; D000959:Antihypertensive Agents; D010080:Oxazoles; D003000:Clonidine; D000077769:Rilmenidine