Dose-dependent effects of D-N-allylnormetazocine on regional cerebral metabolic rates for glucose.
Cerebral metabolic patterns produced by different doses of the benzomorphan opioid drug, D-N-allylnormetazocine (D-NANM), were studied using the 2-deoxy-D-[1-14C]glucose method in rats. The lowest dose of D-NANM (0.5 mg/kg) decreased regional cerebral metabolic rates for glucose (rCMRglc) in areas, such as cranial nerve nuclei, that contain high densities of sigma (sigma) receptors. However, higher doses of the drug (2.7 and 5 mg/kg) increased rCMRglc in components of the extrapyramidal motor and limbic systems. Some of these latter areas (e.g. molecular layer of the dentate gyrus, accumbens nucleus, globus pallidus, ventral posterior nucleus of the thalamus) are not enriched in sigma receptors. Reductions in rCMRglc produced by the lowest dose of D-NANM probably reflect direct interactions of the drug with sigma receptors, whereas increases in rCMRglc observed with the highest doses more likely result from effects of D-NANM on PCP receptors.
della Puppa
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Neuroimaging and Drug Action Section, National Institute on Drug Abuse, Baltimore, MD 21224.
Kimes
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London
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D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D001931:Brain Mapping; D003847:Deoxyglucose / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017478:Receptors, Phencyclidine / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects
D001786:Blood Glucose; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; C012134:SK&F 10047; D003847:Deoxyglucose; D005947:Glucose; D010620:Phenazocine; D010622:Phencyclidine