Behavioral activation

Extractive agent modifies Hquid-phase behavior (activity coefficients) of key components RCM must be of appropriate form for extractive distillation to work. 

No differences in operability and catalyst behavior (activity and deactivation) in the two plants were discernible. The expected catalyst lifetime in a commercial plant, calculated from the movement of the temperature profile down the catalyst bed with time, in both cases will be more than 16,000 hrs under the design conditions. 

Additional in vivo studies on the biological activity of proanthocyani-dins investigating a series of behavioral activities (motihty, body weight gain, body temperature, motoric coordination, anticonvulsant effects and central analgesic activities) showed no or only moderate pharmacological effects [53]. On the other hand, dietary supplementation with cocoa pro-cyanidin supplements can dose-dependently prevent the development of hyperglycemia in diabetic obese mice [54]. 

When a particular behavioral pharmacology is associated with a specific biochemical action within a series of congeners, it is likely that the biochemistry is a functional component of the observed behavioral activity. This is not necessarily the case if only one or a few molecules are available for study they may well possess ancillary biochemical pharmacology that is... 

Huang, J.T., and Ho, B.T. The effect of pretreatment with iproniazid on the behavioral activities of P-phenethylamine in rats. 

Loeomotor aetivity has historically been used as an index of psychostimulant effects. Simple assessment of amount of loeomotor activity can provide the basis for anatomical as well as pharmaeologieal analysis of the neural substrates that mediate the behavioral expression of stimulant action. More sophisticated behavioral measurement systems ean reeord multiple measures of activity and describe spatial and temporal patterning of loeomo-tion. In such systems, qualitative aspects of behavioral activation can be evaluated by examining the entire activity profile. A comparison of the effects of novel drugs with those produced by well-characterized substanees may lead to a better understanding of their mechanisms of action and subjective properties. 

MDMA significantly altered the behavioral activity profile of rats. 

MDMA and MDE also produced locomotor patterns that differed significantly from other stimulants. Previous studies in rats have demonstrated that amphetamine-induced hyperactivity involves complex patterns of widely distributed locomotion with frequent directional changes (Geyer et al. 1986 Geyer et al. 1987). In contrast, similar levels of behavioral activation produced by scopolamine or apomorphine are associated with relatively smooth locomotor paths, in which the same movement patterns are frequently repeated. Other stimulants, such as caffeine or nicotine, increase the amount of locomotor activity without significantly altering its pattern (Geyer... 

So you see, according to our thinking, some of these drugs are more dangerous because the toxic doses are so very close to the behaviorally active therapeutic doses. 

FIGURE 7. Determination of MDA concentration in rat brain following administration of behaviorally active doses of the drug... 

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). 

Albuquerque, E.X. Warnick, J.E. Aguayo, L.G. Ickowicz, R.K. Blaustein, M.P. Maayani, S. and Weinstein, H. Phencyclidine Differentiation of behaviorally active from inactive analogs based on interactions with channels of electrically excitable membranes and of cholinersic receptors. In Kamenka, J.M. Domino, E.F. and Geneste P., eds. Phencvclidine and Related Arvl hexvl ami nes Present and Future Appl i cat ions. Ann Arbor ... 

Antidepressant medications appear to be useful for certain children and adolescents, particularly those who have severe or psychotic depression, fail psychotherapeutic measures, or experience chronic or recurrent depression. SSRIs generally are considered the initial antidepressants of choice, although comorbid conditions may favor alternative agents. Clinicians should be aware of the possibility of behavioral activation with the SSRIs, including such symptoms as impulsivity, silliness, daring conduct, and agitation.44 Desipramine should be used with caution in this population because of several reports of sudden death, and a baseline and follow-up electrocardiogram (ECG) may be warranted when this medication is used to treat pediatric patients.9... 

Regarding the adrenal steroids, the behavioral activation of hormonal secretion in stress is part of a mechanism for restoring homeostatic balance. For example, an encounter with a predator may require rapid evasive action, in which neural activity and rapidly mobilized hormones such as epinephrine play a role. Adrenal steroid secretion is slower, reaching a peak minutes after the stressful event, and therefore is not expected to play a role in coping with the immediate situation. If the evasive action is successful and... 

No perceptible effect on goose behavior (activity, pecking rate) after spraying. Maximum residues in herbage were 20.4 mg/kg 3 days after spraying and 10 mg/kg FW in goose feces 4 days after spraying residues were <0.05 mg/kg within 10 days (Clements et al. 1992)... 

Cyclic analogs of DMT and DET, i.e, 43 and 44, respectively, have been synthesized the aziridine 43 appears to possess activity as a CNS depressant (171), while the pyrrolidine 44 displays some behavioral activity. Compound 44 was active in Hall s open-field test but was less active than DET (38) (23). In attempts to measure hyperthermic activity, 44 was found to be rather toxic in rabbits (111). Oddly enough, no cyclic analog has ever shown activity/potency comparable to its acyclic counterpart. Thus, based only on scant animal data, cyclization of the lower dialkyl homologs apparently does not lead to marked behavioral activity. 

N,N-Dialkyltryptamines bearing an alkyl substituent on the aromatic nucleus have not been evaluated in man, and only data from animal studies are available. Taborsky et al. (228) found 1-methylation to have variable effects on behavioral activity. This might reflect blood-brain barrier permeability. Methylation at the N1 position of DMT (37), to give 1, N,N-trimethyltryptamine (1-TMT), had... 

Bufotenine has been found to be behaviorally inactive, or only weakly active, in most animal studies, although at 15 mg/kg, it did produce the head-twitch resonse in mice (43). It was also behaviorally active in experiments in which the blood-brain barrier was bypassed (78). Acylation of the polar hydroxy group of bufotenine increases its lipid solubility (65,74) and apparently enhances its ability to cross the blood-brain barrier (64). For example, O-acetylbufotenine (5-acetoxy-N,N-dimethyltryptamine 54) disrupted conditioned avoidance behavior in rodents (65) and produced tremorigenic activity similar to that elicited by DMT (37) or 5-OMeDMT (59) when administered to mice (64). In this latter study, a comparison of brain levels of bufotenine after administration of O-acetylbufotenine with those of DMT and 5-OMeDMT revealed bufotenine to be the most active of the three agents, based on brain concentration. The pivaloyl ester of bufotenine also appears to possess behavioral activity, since stimulus generalization was observed when this agent was administered to animals trained to discriminate 5-OMeDMT from saline (74). 

There are only two reports of the human evaluation of a 6-hydroxylated N,N-dialkyltryptamine. Szara and Hearst (223) studied the effects of 6-hydroxy-N,N-diethyltryptamine (6-OH-DET 56) in a single subject. Doses of 1 and 2 mg were inactive a 5-mg dose produced a short-lasting perceptual disturbance and a 10-mg dose, after 1 hr, produced some psychotomimetic disturbances. Rosenberg et al. (182) compared the activity of DMT with that of 6-OH-DMT (55) in five human subjects. While DMT was active, the 6-hydroxy derivative was found to be inactive at intramuscular doses of approximately 50 to 75 mg. At a dose of 10 mg/kg, 6-OH-DMT (55) increased spontaneous activity in mice more so than a comparable dose of DMT 6-OH-DET (36) was essentially equiactive with DET in this respect (224). In most other animal studies, however, 6-hydroxylation of DMT has been observed to result in a decrease or complete loss of behavioral activity (228,236-238). The behavioral potency of 5-OMeDMT (59) was also reduced by 6-hydroxylation (226). 7-Hydroxy-N,N-dimethyltrypt-amine (7-OH-DMT 57) has not been evaluated in man. At an intraperitoneal dose of 33 jtM/kg, 7-OH-DMT displayed no behavioral effects in rats (228). The pharmacologic effects of all four hydroxylated derivatives of DMT, psilocin (49), bufotenine (53), 6-OH-DMT (55), and 7-OH-DMT (57) have been compared in studies by Taborsky et al. (228) and by Cerletti et al. (29). 

Alpha-methylation of DMT reduced its behavioral activity in animals, while alpha-methylation of N-methyltryptamine (27) resulted in an agent with stimulant properties (137,228). Alpha-methyltryptamine (a-MeT structure 77), however, is hallucinogenic in man at doses of about 30 mg. Thus it is two to three times more active than DMT (for review see refs. 24, 81, and 196). 5-Methoxy-a-methyltryptamine (5-OMe-a-MeT 78) was also determined to be twice as active in man as its dialkyl counterpart, 5-OMeDMT. In human trials, 5-OMe-a-MeT produced behavioral effects at about 3 mg (204). A comparison of the activities of the individual isomers of 78 in man has not been reported. However, Glennon and co-workers (76,83,90) found that the (+)-isomers of both a-MeT and 5-OMe-a-MeT are more active than their racemates in tests of discriminative control of behavior in rats. Although (+)-5-OMe-a-MeT was four times more active than its enantiomer, (-)-a-MeT did not produce effects similar to either racemic a-MeT or 5-OMeDMT. 

Taken together, the data presented here show that many phenyl- and in-dolealkylamines are hallucinogenic in man and behaviorally active in animals. In both series, primary amines penetrate the blood-brain barrier with difficulty, although this seems to be more of a problem with tryptamines (and even N-monoalkyltryptamines) than with phenethylamines. This situation is somewhat alleviated in the presence of an alpha-methyl substituent. The primary amines are also prone to rapid metabolism by oxidative deamination. Metabolism, however, can be impeded by the presence of an alpha-methyl or N-alkyl function. 

Glennon, R. A., Young, R., and Jacyno, J. M. (1983) Indolealkylamine and phenalkylamine hallucinogens Effect of a-methyl and N-methyl substituents on behavioral activity. Biochem. Pharmacol., 32 1267-1273. 

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