The major hallucinogens and the central cytoskeleton: an association beyond coincidence? Towards sub-cellular mechanisms in schizophrenia.
There appears to be a remarkably consistent structural and functional relationship between the phenylethylamine hallucinogens and the microtubule inhibitor colchicine. Such a relationship is not sustained in simple form through to the indoleamine hallucinogens and the indole based Vinca alkaloids. However, LSD and the more potent hallucinogens retain the full potential to disrupt the structure of the brain's cytoskeleton indirectly via serotonin and the raphe system. Serotonin appears to have a direct role in regulating and maintaining microtubules and microfilaments. It appears that a second receptor mediated action is required for full hallucinogenic activity. It is deduced that cytoskeletal restraints may have a role in governing central information processing. A theory for the cellular mechanisms of thought disorder and drug induced hallucinations is proposed. Schizophrenia may reflect a subtle disorder of central cytoskeletal function.
van Woerkom
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AE
University of Cambridge Clinical School, Addenbrooke's Hospital, UK.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology; D003599:Cytoskeleton / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D006213:Hallucinogens / Q000633:toxicity*; D006801:Humans; D007696:Kindling, Neurologic / Q000502:physiology; D008090:Lisuride / Q000633:toxicity; D008954:Models, Biological; D010627:Phenethylamines / Q000633:toxicity; D012559:Schizophrenia / Q000209:etiology* / Q000503:physiopathology; D012701:Serotonin / Q000502:physiology; D013329:Structure-Activity Relationship
D006213:Hallucinogens; D010627:Phenethylamines; D012701:Serotonin; D008090:Lisuride; D004298:Dopamine