Differential effects of prazosin and yohimbine on fentanyl-induced muscular rigidity in rats.
Whereas muscular rigidity is a well-known phenomenon that is related to anesthesia induced by large doses of narcotic drugs, the precise underlying mechanism(s) remain to be fully elucidated. This study investigated the possible role of noradrenergic neurotransmission and the participation of alpha-adrenoceptors in this phenomenon. Male Sprague-Dawley rats, under ketamine-induced anesthesia (120 mg/kg, i.p.) and with proper control of respiration, body temperature and end-tidal CO2 were used. Intravenous administration of fentanyl (100 micrograms/kg) consistently caused a significant increase in the electromyographic (EMG) activity, recorded from both gastrocnemius and abdominal rectus muscles. This implied muscular rigidity was markedly antagonized by pretreatment with the specific alpha 1-adrenoceptor blocker, prazosin (50 or 250 micrograms/kg, i.v.). This antagonism occurred in spite of a high level of fentanyl in the plasma, as determined by radioimmunoassay. The specific alpha 2-adrenoceptor blocker, yohimbine (1.15 or 2.3 mg/kg, i.v.), on the other hand, not only failed to prevent fentanyl-induced activation of the EMG, but actually potentiated the response. It is concluded that noradrenergic neurotransmission, possibly originating from the locus coeruleus, may participate in the elicitation of muscular rigidity by fentanyl. Furthermore, this process may involve an excitatory action through alpha 1-, and an inhibitory action through alpha 2-adrenoceptors, in the spinal cord.
Tsou
M Y
MY
Department of Anesthesiology, Veterans General Hospital, Taipei, Taiwan, Republic of China.
Lui
P W
PW
Lee
T Y
TY
Pan
J T
JT
Chan
S H
SH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004576:Electromyography; D005283:Fentanyl / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009127:Muscle Rigidity / Q000139:chemically induced* / Q000503:physiopathology; D009132:Muscles / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology*
D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D005283:Fentanyl; D011224:Prazosin