Psychotomimetic activity

Anderson, G.M. Braun, G. Braun, U. Nichols, D.E. and Shulgin, A.T. Absolute configuration and psychotomimetic activity. In Barnett, G. Trsic, M. and Willette, R., eds. Quasar Quantitative Structure Activity Relationships of Analgesics, Narcotic Antagonists, and Hallucinogens. National Institute on Drug Abuse Research Monograph 22. Rockville, MD the Institute, 1978. pp. 8-15. 

If the behavioral activity of PCP is related to its block of pre-synaptic K channels (Albuquerque et al. 1981 Albuquerque et al. 1983 Blaustein and Ickowicz 1983), PCP-like analogues should block these same K channels with a rank order of potency that parallels their relative in vi vo psychotomimetic activity. One of the most behavioral ly potent PCP-like agents is TCP (1 -[1 -(2 -thienyl)-cyclohexyl] piperidine) (Shannon 1983). Figure 4 illustrates the dose-response curves for the block of components S and T by this drug. The data indicate that TCP is a more potent blocker of Sv than is PCP (figure 2). TCP blocked component T only at high concentrations (>10 5M), and in this respect was approximately equivalent in potency to PCP (figure 2). 

Clinical trials of some of the more potent tertiary amines revealed these to exhibit marked psychotomimetic activity.11 Much subsequent work thus dealt with the quaternary salts which do not reach the central nervous system. Many of the uses of anticholinergic drugs involve "topical" application (e. g., interior of the stomach, intestine or bronchi) ... 

Szara and co-workers (221,223,225) noted psychotomimetic activity for N,N-diethyltryptamine (DET 38) at a dose of 1 mg/kg. In at least one study (223), the effects of DET were found to be unpleasant. In a study involving 71 subjects, DET produced behavioral effects at intramuscular doses of approximately 50 mg (0.65 to 0.85 mg/kg) (19). The duration of action of DET was somewhat longer (about 3 hr) than that of DMT. Interestingly, some subjects in the latter study reported, in contrast to Szara s findings, that DET produced a euphoric effect. Szara has suggested that this might be a dose-related phenomenon. 

Barfknecht, C. F., Nichols, D. E., and Dunn, W. J., Ill (1975) Correlation of psychotomimetic activity of phenethylamines and amphetamines with l-octanol/water partition coefficients. J. Med. Chem., 18 208-210. 

The advances in isolation methods made possible a clarification of the chemistry of cannabis. In 1963, our group reisolated CBD and reported its correct structure and stereochemistry. A year later we finally succeeded in isolating pure A -tetrahydrocannabinol (A -THC), elucidated its structure, obtained a crystalline derivative and achieved a partial synthesis from CBD. Several years later, a minor psychotomimetically active constituent, A -THC, was isolated from marijuana. Whether this THC isomer is a natural compound, or an artifact formed during the drying of the plant, remains an open problem. 

Progesterone, 164 Proglumide, 93 Propanidid, 79 Propenzolate, 75 Propizepine, 472 Propoxyphene, 57 Propranolol, 105, 107, 212 Proquazone, 386 Proquinolate, 368 Prorenone, 175 Prostalene, 5 Proxazole, 271 Purine synthesis, 467 Psilocybine, 342 Psychotomimetic activity, 71... 

The first drug in this class was nalorphine (/V-allylmorphine). Nalorphine is equipotent with morphine but produced severe psychotomimetic activity, which precluded its use as an analgesic. Until the discovery of naloxone it was widely used for its antagonist properties in the treatment of opioid overdose. The dysphoric side effects of some of this class of drugs is thought to be due to binding to the non-opioid a receptor. 

Hochstein and Paradies (1957) suggest that, in addition, the alkaloids harmaline and d-tetrahydroharmine, discovered in B. caapi, "may have substantial psychotomimetic activity in their own right."... 

In mammals 5-hydroxytryptamine is found in the brain, in the blood, and in the tissues of the stomach, intestines, and lungs its function in all these sites has not yet been fully elucidated. However, there is little doubt that it plays an extremely important role in the central nervous system, and, in particular, in the brain. The psychotomimetic activity of some drugs appears to be due to interference with the function of 5-hydroxytryptamine in the brain. It is also implicated in certain... 

Fusek, J., Kabes, J., Fink, Z. (1971). Peripheral effects of anticholinergic psychotomimetics. Activ. Nerv. Sup. 13 191-3. 

The great avidity of mitochondria from rat brain for 3-qulnuclldlnyl benzllate has been mentioned previously (56). Lareson et al. (192) recorded the Infrared spectra of seven esters of benzllic acid, of ei t esters of 3-qulnuclidlnol, and of atropine and scopolamine and attempted to correlate the relative strengths of the intramolecular hydrogen bond with the threshold doses of the various compounds in producing psychotomimetic effects in dogs. The data of Albanus (42) on the psychotomimetic activities of anticholinergic compounds were used for the comparison. Of the esters of benzllic acid. 

Gershon and Angrlst (247) summarized fch research that had been done vlth Ditran and other anticholinergic psychotomimetic compounds and with possible antagonists of their psychotomimetic activities Nothing particularly new was reported In this paper. Tacrine is regarded as the best overall antagonist. 

Barfknecht, C.F. Nichols, D.E., Dunn, W.J., III. Correlation of Psychotomimetic Activity of Phenethylamines and Amphetamines with 1-Octanol-water Partition Coefficients. J Med Chem, 18 208-210,1975. 

If the results reported here can be confirmed by others, a clinically useful nonaddicting potent analgesic will have been attained. More significantly, the means by which other similar compounds may be identified in this and other chemical groups will now be apparent. Having thus far dissociated addiction liability and psychotomimetic activity from potent analgesia, it may now be... 

Our studies have also invalidated the hypothesis that the lone pair of nitrogen electrons in glycollate bases are essential to anticholinergic and psychotomimetic activity (Abood, 1970 Gabel and Abood, 1965), since quaternary salts were more active than the hydrochlorides and there was no evidence that central effects were caused by a significantly different mechanism from peripheral effects. 

Many of the substances which are known to have psychotomimetic effects in man, such as lysergic acid diethylamide (LSD) and certain tryptamine derivatives, contain an indole moiety. Mescaline, however, does not contain such a moiety despite its psychotomimetic activity, but it has been suggested by various authors that the side chain of the mescaline molecule might fold back towards the benzene ring to resemble the indole nucleus of LSD and thereby impart psychotomimetic activity. 

D. Other- Studies continued on the measurement of physical chemical parameters In order to elucidate structure activity patterns in psychotomimetic compounds. Thus X-ray, nmr° and total orbital energies were used to study molecular conformation and its relationship to psychotomimetic activity in the lysergic acid series. The conformations of psilocin and mescaline were examined by molecular orbital and classical potential function calculations. . Correlations of tiv spectra, native fluorescence and association constants " vrlth the psychotomimetic activity of various methoxylated phenylisopropylaralnes were made. Quantum mechanical studies of... 

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