Analgesic potency of a new anticonvulsant drug versus acetylsalicylic acid via laser somatosensory evoked potentials. Randomized placebo-controlled double-blind (5-way) crossover study.
A randomized, double-blind crossover study was performed with three different acute oral dosages of CM 40907 (3-(4-hydroxypiperidyl)-6-(2'-chlorophenyl)-pyridazine) (600, 900 and 1200 mg), a newly developed anticonvulsant drug, vs acetylsalicylic acid (ASA, 1000 mg) and placebo in 12 male healthy volunteers to check analgesic potency. Objective algesimetry was done by Laser Somatosensory Evoked Potentials (LSEP). Subjective pain intensities were measured by retrospective visual analog scale ratings (VAS). Effects on objective vigilance were checked by Auditory Evoked Potentials (AEP). For both types of evoked potentials there was a simultaneous control of alterations in vigilance by means of the adaptive pursuit tracking task (APTT). A vigilance-controlled EEG (V-EEG) and a resting (R-EEG), visual analog scales (VAS) on sedation, excitation and anxiety as well as vital parameters (blood pressure and heart rate under supine and upright conditions) and adverse event scales were included in this trial as well. CM 40907 showed distinct analgesic effects on objective and subjective algesimetric parameters, which for the highest dosage (1200 mg) were superior in ("central") P2-amplitude suppression of LSEPs to those of ASA in ("peripheral") N1-amplitudes suppression and ongoing for more than 6 h. Subjective sedation was decreased, however, AEP-findings indicated a decreased vigilance after CM 40907. Some EEG-patterns, specifically related with CM 40907--although being ambiguous in classification terms--resembled features of benzodiazepines. Blood pressure and heart rate were raised in a clinically irrelevant manner.
Schaffler
K
K
Institute for Pharmacodynamic Research, Munich, Fed. Rep. of Germany.
Wauschkuhn
C H
CH
Gierend
M
M
D000161:Acoustic Stimulation; D000328:Adult; D000700:Analgesics; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004311:Double-Blind Method; D004569:Electroencephalography; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007834:Lasers; D008297:Male; D008568:Memory / Q000187:drug effects; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D011597:Psychomotor Performance; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology*
D000700:Analgesics; D000927:Anticonvulsants; D011724:Pyridazines; C045387:CM 40907; D001241:Aspirin