Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of ethylketazocine (EKC) administered intraperitoneally and the nicotinic ligands (-)- and (+)-nicotine, (-)-cytisine, (-)-lobeline, and (+)-2-methylpiperidine administered into the 4th ventricle on the latency of the thermally evoked withdrawal reflex of the decerebrate rat were investigated. EKC administered intraperitoneally produced both hyperalgesia and analgesia. (-)-Nicotine administered into the 4th ventricle produced a biphasic dose related effect on the latency of the withdrawal reflex; low doses produced a dose related analgesia while higher doses produced hyperalgesia. (-)-Cytisine and (-)-lobeline administered into the 4th ventricle produced biphasic effects. (+)-2-Methylpiperidine administered into the 4th ventricle produced a significant degree of hyperalgesia. Both the analgesic and hyperalgesic effects of (-)-nicotine were antagonized by mecamylamine (1 mg/kg) and naltrexone (5 mg/kg). The hyperalgesic action of (+)-2-methylpiperidine was antagonized by naltrexone but not by mecamylamine. These observations suggest that there are both medullary opioidergic and nicotinic cholinergic mechanisms for modulating both analgesic and hyperalgesic processes and that nicotinic ligands have multiple mechanisms of action in the brain.
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PMID:Opioid and nicotinic medullary hyperalgesic influences in the decerebrated rat. 290 Nov 13

Four distinguishable nicotinic binding sites have been identified as well as four nicotinic ligands with different specificities: (+/-)-2-methylpiperidine which binds to a very high affinity site (Site 1) and produces up-regulation of the high affinity site (Site 2); (-)-nicotine which binds to Site 1 and Site 2 as well as to a low affinity site (Site 4); (+)-nicotine which binds to Site 1, Site 4 and Site 3 which is also a high affinity site; and (-)-cytisine which binds to Sites 1 and 2. These drugs were injected into the 4th ventricle of 5 dogs in graded concentrations (12.5 to 400 micrograms) and their effects on the EEG, skin twitch reflex latency, heart rate, rectal temperature, pupillary diameter, blood pressure and the amplitude of the flexor reflex were measured. Drugs which act predominantly on Site 1 [(+/-)-2-methylpiperidine and (+)-nicotine] produced EEG synchronization and hyperalgesia while drugs which interact with Sites 2 and 4 produce EEG desynchronization, analgesia and tachycardia. These data indicate that nicotinic ligands which have different binding specificities have different actions in medullary function and support the hypothesis that the different binding sites have different pharmacologic significance.
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PMID:Fourth ventricle effects of nicotine, 2-methylpiperidine and cytisine in dogs. 378 43