Peripheral Sympatholytic Effects of l-α-Acetylmethadol

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Abstract
1-alpha-Acetylmethadol (LAAM), 1.4 mg/kg or greater, decreased the response of the cat nictitating membrane to pre- and postganglionic sympathetic nerve stimulation. LAAM had a greater effect on the low-frequency (0.5 Hz) than on the high-frequency (5-20 Hz) responses. No difference was observed between the effects of LAAM on the pre- as opposed to the postganglionic responses. The responses ot the nictitating membranes to intravenous epinephrine were not affected by LAAM. LAAM appears to act at the nerve terminal. The minimum dose of LAAM (1.4 mg/kg) which decreased the nictitating membrane responses also decreased blood pressure and heart rate. Naltrexone, 300 micrograms/kg, s.c., antagonized the effects of LAAM on the nictitating membrane responses and the cardiovascular actions of the drug. In anesthetized dogs, naltrexone completely blocked the blood pressure response to LAAM and partially blocked the effects of LAAM on heart rate and contractile force. The data suggest that LAAM may produce its cardiovascular effects, in part, by an action on the peripheral sympathetic nervous system which involves opiate binding sites. LAAM also appears to have direct actions on the heart to decrease heart rate and contractile force that do not involve opiate binding sites.

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