Effect Of Mescaline Research Articles

NOVEL STRUCTURAL HYBRIDS OF MESCALINE WITH PCP-ANALOGS: POTENTIAL ANTAGONISTS FOR CENTRAL PCP-RECEPTORS

The possible involvement of the synclinal conformation of mescaline with phencyclidine (PCP)-receptors has promoted the synthesis of certain novel structural hybrids of mescaline with PCP-analogs. The effect of mescaline and the potential antagonisticactivity of the newly proposed derivatives at central PCP-receptors of albino rat brains will await investigation. The suggested compounds were chemically 1-aryl-1-(3,4,5-trimethoxy; or trihydroxy) phenethylamino; or N-substituted-phenethylamino cycloalkanes. An N-(2-chloroethyl) moiety was, also incorporated into some of the designed analogs for exploration of the possible participation of such alkylating arm to the elicited activity.

The effect of mescaline, 3,4-dimethoxyphenethylamine and 2,5-dimethoxy-4-methylamphetamine on rat plasma prolactin: Evidence for serotonergic mediation

Mescaline, 3,4-dimethoxyphenethylamine (DMPEA) or 2,5-dimethoxy-4-methylamphetamine (DOM) was administered to male Sprague-Dawley rats, alone or in combination with para-chlorophenylalanine (PCPA), an inhibitor of serotonin (5-HT) synthesis, or methysergide, a 5-HT receptor blocker. All three compounds increased plasma prolactin (PRL) levels. These increases were potentiated by PCPA and blocked by methysergide. Pretreatment with alpha-methylparatyrosine (AMPT), an inhibitor of catecholamine synthesis, resulted in an increase in plasma PRL equal to the additive effects of the independent administration of mescaline, DMPEA, or DOM plus the AMPT-induced response. The results suggest that mescaline, DMPEA and DOM may be exerting their effects on rat plasma PRL through direct stimulation of serotonin receptors. These results further demonstrate the ability of PCPA to rapidly induce supersensitivity of the 5-HT receptors which stimulate PRL secretion.

Behavioral disinhibition by mescaline

Rats were exposed to a CER procedure in which sucrose drinking was suppressed by a tone previously paired with shock. Suppression of drinking during the tone was reduced by mescaline (50 mg/kg) independently of whether training took place under mescaline or placebo. Additional data on the effect of mescaline on sucrose drinking indicated that the result could not be attributed to an increased drive to drink sucrose. It was proposed that mescaline releases behavior from inhibitory control. A number of studies from the literature were cited which supported this hypothesis.

Development of tolerance to the antinociceptive effect of mescaline intraventricularly administered to rabbits.

Some effects of intraventricular injection of mescaline are examined in conscious rabbits. By means of electrical stimulation of the tooth pulp it is shown that an acute treatment with 70, 100, 150 mug/kg of mescaline elicits analgesia, the intensity of which is dose-dependent: with daily administration of 100 mug/kg for 5 days a complete tolerance develops to the antinociceptive effect. A tolerance also develops to the behavioral effects of mescaline after repeated administrations, with the exception of the stuporous state, a symptom which, on the contrary, is accentuated as the treatment proceeds. An EEG arousal is induced in the rabbit by acutely administered mescaline; the chronic treatment (100 mug/kg) makes the return of voltage to original levels progressively slower. Finally, the confrontation of certain of the mescaline-induced effects with those of morphine suggests some biochemical and neural patterns common to the 2 drugs.

Relationship of the structure of mescaline and seven analogs to toxicity and behavior in five species of laboratory animals

The effect of mescaline and of 7 mescaline analogs (3,4-dimethoxy- β -phenylethylamine; 3,4-methylenedioxy- β -phenylethylamine; 3,4-methylenedioxy- α -methyl- β -phenylethylamine; 3,4-methylenedioxy- α -ethyl- β -phenylethylamine; 3,4-dimethoxy- α -methyl- β -phenylethylamine; 3,4,5-trimethoxy- α -methyl- β -phenylethylamine; and 3,4-methylenedioxy- N,α -dimethyl- β -phenylethylamine) has been studied in the mouse, rat and guinea pig following ip administration and in the mongrel dog and rhesus monkey following iv administration. The LD50 value for each agent has been determined in each species. For 7 of the 8 drugs tested the LD50 value is significantly lower in the rat than in the mouse or guinea pig. A comparison of the observable signs of drug action in the dog and monkey shows the dog to be the preferred species for evaluating the effects of these agents. The relevant literature regarding the actions of the drugs has been reviewed. Modifications in the mescaline structure which are represented by the 7 analogs and which alter pharmacologic activity include: decreased potency following removal of the 5-methoxy group or N-demethylation, and increased potency following alpha substitution on the side chain or introduction of the 3,4-methylenedioxy group.

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on ribosomal synthesis of poly-uridine-directed polyphenylalanine.

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on ribosomal synthesis of poly-uridine-directed polyphenylalanine.

Some neurochemical and neuropharmacological studies on the interactions between mescaline and 1-methyl-1,2,5,6-tetrahydropyridine-3-(N,N-diethylcarboxamide) (THPC).

The effect of THPC was studied on some pharmacological and neurochemical changes induced in the rat by mescaline. The results show that THPC antagonizes the effect of mescaline on the calorigenic action of a methyl-m-tyrosine in reserpinized mice. THPC potentiated the depletion of brain dopamine caused by H77/77 in combination with mescaline. In none of the other pharmacological or neurochemical tests was there any evidence that THPC antagonized or potentiated the effects of mescaline.

Effect of mescaline on single cortical neurones.

The effects of mescaline upon single cortical neurones were studied, using the microiontophoretic technique. Mescaline elicited excitatory and depressant responses similar to those evoked by noradrenaline (NA) and 5-hydroxytryptamine (5-HI). The responses to NA and mescaline were usually in the same direction, the neurone being either excited by both drugs or depressed by both drugs. The correlation between the effects of mescaline and 5-HT, however, was less consistent. The beta-adrenoceptor blocking agent MJ-1999 and the 5-HT antagonist methysergide were both effective in antagonizing mescaline responses.

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the stability of brain-cortex ribosomes

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the stability of brain-cortex ribosomes

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the hydrogen-bonded structure of ribonucleic acid of brain-cortex ribosomes

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the hydrogen-bonded structure of ribonucleic acid of brain-cortex ribosomes

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the stability of brain-cortex ribosomes.

1. During the action of mescaline sulphate on goat brain-cortex slices the ribosomal particles become susceptible to breakdown, releasing protein, RNA, acidsoluble nucleotides and ninhydrin-positive materials, resulting in loss of ribosomal enzyme activities. 2. Ribosomes of the mescaline-treated cortex slices undergo rapid degradation in the presence of trypsin and ribonuclease. 3. Mescaline does not alter the chemical and nucleotide compositions or the u.v.-absorption characteristics of ribosomal particles, however.

Mescaline-induced changes of brain-cortex ribosomes. Effect of mescaline on the hydrogen-bonded structure of ribonucleic acid of brain-cortex ribosomes.

1. The action of mescaline sulphate on the hydrogen-bonded structure of the RNA constituent of ribosomes of goat brain-cortex slices was studied by using the hyperchromic effect of heating and formaldehyde reaction. 2. The ribosomal total RNA species of the mescaline-treated brain-cortex slices have a smaller proportion of hydrogen-bonded structure than the ribosomal RNA species of the untreated brain-cortex slices. 3. Mescaline also appears to have affected this lowering of hydrogen-bonded structure of the ribosomal 28S RNA of brain-cortex tissue.

Effect of Mescaline on Nicotinamide Adenine Dinucleotide Synthesis in the Central Nervous System

Nicotinamide adenine dinucleotide (NAD) synthesis in mouse brain was demonstrated following the intracerebral injection of nicotinamide (500mg./Kg.). Animals which received mescaline hemisulfate (100mg./Kg.) 90min. prior to nicotinamide were found to have higher levels of brain NAD at the 2 and 3hr. time intervals.

Interaction of "stress" and the response to mescaline.

THE clinical effect of mescaline is very variable both between different subjects and in the same subject at various times. One factor that has been noted to play a part here is the anxiety proneness of the subject. Klerman1 has shown in a double blind study that passive, anxious, intellectual introverts react in a far more psychotic manner to mescaline than do non-anxious extroverts. Our clinical experience confirms this.

Effect of Mescaline on Cardiopulmonary Dynamics: Method for Determination of Right Ventricular Pressure in the Guinea Pig

The effect of mescaline on respiratory dynamics, right ventricular pressure, and the ECG in the guinea pig is presented. A procedure for the acquisition of normal right ventricular pressure is described. The mean value for the latter was 13.4 ± 4.6 mm. Hg. Mescaline in low dosages (1 to 20 mg./Kg.) produced a slight increase in heart rate; higher dosages (50 to 240 mg./Kg.) induced bradycardia and conduction disturbances. Respiratory rate, resistance of the airways, and minute volume increased significantly, while tidal volume and compliance decreased. The decrease in compliance was near maximum (−70 and − 77 per cent) with high dosages (50 and 100 mg./Kg.). Right ventricular pressure increased, average 45 per cent, following moderate dosages of mescaline (25 mg./Kg.). Diphenhydramine and chlorpheniramine (range 0.4 to 0.7 mg./Kg.) in sufficient concentration to block the effect of histamine (4 mg./Kg.) were utilized to observe possible mescaline antagonistic activity. However, the antihistamines were ineffective against mescaline. It appears probable that mescaline does not owe its activity on these parameters to histaminic receptor stimulation.

Structure-activity relationship studies on mescaline: the effect of dimethoxyphenylethylamine and N:N-dimethyl mescaline on the conditioned avoidance response in the rat.

Structure-activity relationship studies on two mescaline analogues have been conducted, using rats trained on a CAR buzzer-shock schedule. 3∶4-dimethoxyphenylethylamine has been shown to depress the CAR with an apparent bimodal distribution of peak activities, in contrast to the biphasic inhibitory and excitatory effect of mescaline. The effect of this dimethoxy compound is similar to that previously reported for a protein fraction from schizophrenic plasma; this is of particular interest as six groups have recently reported the isolation of this compound from schizophrenic urine. The effect of N:N-dimethylation of mescaline is to abolish its inhibitory action on the CAR and to augment its excitant action. The significance of these findings is discussed.

The effect of mescaline upon the conditioned avoidance response in the rat.

Seventeen male hooded rats were trained on a CAR schedule in a shuttle box, using sound as the CS and shock as the US. After training, nine animals were injected intraperitoneally with 25 mg/kg mescaline hydrochloride, and eight animals with 25 mg/kg followed by 12.5 mg/kg. The results were recorded in terms of the number of shocks received, the number of crossings made and the reaction time from the onset of the CS. The results showed that mescaline exerted a biphasic effect, initially depressing the CAR, and then giving rise to a prolonged excitatory phase. When the experimental series was repeated two weeks later, it seemed that, although the behavioural pattern was basically the same some. tolerance of the drug had persisted. Further tests showed that this tolerance has disappeared eight weeks after the last injection. The smaller dose depressed the CAR less, and in fact the CAR was not depressed in less sensitive (Class II) animals, whereas the excitatory phase was increased and significantly so in Class II animals.

134 The effect of mescaline on the optic evoked potential

134 The effect of mescaline on the optic evoked potential

The Effect of Mescaline and Yohimbine on the Respiration of Rat Brain Homogenate

By manometric method using conventional Warburg apparatus, the oxygen uptake of rat brain homogenate in glucose, glutamate, and succinate was found to be inhibited by mescaline and yohimbine. Yohimbine inhibited the brain homogenate's respiration in glucose considerably more than it did the respiration in glutamate and in succinate. Mescaline inhibited the homogenate's oxygen uptake in glucose, in glutamate, and in succinate to a similar degree, when the drug and the substrate were added to the brain homogenate at the same time. This is in contrast to the lack of mescaline inhibition of the succinate respiration of chopped brain preparation which was incubated with the drug for two and one-half hours before addition of substrate, as reported by previous investigators.

Effect of mescaline and L.S.D. on evoked responses especially of the optic system of the cat

Mescaline chloride (in solutions up to 33 per cent by weight) was applied topically to the cortex and lateral geniculate of the cat and its effect on evoked responses was studied. Responses were evoked by local cortical stimulation and from appropriate sensory receiving areas by flash stimuli to the eye, both of white and of four colors; click to the ear; and electrical stimulation to the sciatic nerve. With all types of stimuli mescaline had the same marked effect on amplitude and latency of evoked cortical potentials. The effect appeared within 5 min., reached its maximum at about 30 min. and declined after 2 to 4 hours. The amplitude was increased up to 30 times and this was attributable to an increase in the amplitude of a second component of the response. The first component increased two- to threefold or might even be slightly decreased. The maximal response was obtained with stimuli of all intensities and in the visual system with light of all colors. The latency was prolonged to light flash and to direct cortical stimulation. The latency to sciatic and to acoustic stimulation was not changed. Responses were evoked only by adequate stimuli; no responses were evoked from visual cortex by other than visual stimuli, and visual stimuli evoked responses only from known optic receiving areas. When the cortical effect was fully developed, large (2 mV.) spontaneous spikes appeared. At lateral geniculate, mescaline produced a two- to fourfold increase in all components of the response to light flash. Latency was not altered. Local strychnine (3.5 per cent) produced qualitatively the same effect as mescaline on evoked responses to light flash but the effect was more marked in that the amplitude of the response was greater and the full effect developed more quickly. In other respects—increase in latency, increase in amplitude of a second component of the response, “all or none” response to every stimulus and evokation of spontaneous spikes — strychnine and mescaline acted identically on evoked responses to light flash. Intravenous mescaline in doses up to 15 mg. per kg. produced immediate, temporary autonomic changes consisting of cardiac irregularity, periods of apnoea, piloerection, urination and defecation. There was a slight decrease in the amplitude and increase in the duration of cortical and geniculate potentials evoked by light flash. Topical and intravenous lysergic acid diethylamid (up to 9 per cent solution by weight, or 40 μg. per kg.) produced no clear cut effect comparable to that of mescaline on evoked response amplitude. The time interval between the first and second components of the cortical response was prolonged.