Number Facility Test

Sidell and Groff (1974) reported that volunteers dosed with VX (1.5 /rg/kg, i.v.) exhibited a significant decrement in performance on a number facility test within 1 hr after treatment. Bowers et al. (1964) reported anxiety, psychomotor depression, intellectual impairment, and unusual dreaming in volunteers exposed to VX dermally and in whom RBC-ChE was depressed 70% or greater. 

Kltzes et al. (154) analyzed the records of 18 subjects who had been given Intramuscular Injections of atropine at 32-125 ug/kg and who weighed 57.2-90.0 kg. The results on the Number Facility Test (completion of as many additions as possible during 3 min) were used to grade each subject s response to the drug. No correlation between body size and decrease In the Number Facility Test was found. 

The subjects treated with physostlgmlne 30 min after the injection of scopolamine Improved dramatically and rapidly In their performance of the Number Facility Test. These men relapsed into delirium about 3 h after administration of physostlgmlne and then recovered at about the same rate as the untreated men. The effects of physostlgmlne on heart rate and pupil diameter were similar to those In the group treated earlier In the Intoxication. 

The combination of loss of sleep for one night and scopolamine at 10 Mg/kg had a more than additive effect on performance In the Number Facility Test and considerably more effect on manual dexterity chan the scopolamine alone. The combination also produced hallucinations In about 2.7 times as many subjects as the same dose of scopolamine alone. The results with the lover dose of scopolamine were similar to chose reported above, but less striking. The men deprived of sleep for two nights became so somnolent after the dose of scopolamine chat the tests could not be run. 

The performance of each subject on the Number Facility Test after Injection was compared with his scores on the three validity scales and 10 standard scales of the Minnesota (hiltlphaslc Personality Index (MMPl). The best correlations between performance In the Number Facility Test and scores on scales In the MMPI for the men given atropine at 62 Mg/kg were with those In the h/pochondrlasls and mania scales. The best correlations for the men given atropine at 104 g/kg were with scores In the lie and mania scales. For the men given scopolamine at 11.8 pg/kg, the best correlations were with scores In the hypochondriasis and lie scales. If atropine and scopolamine are taken as representative of the group of tropic acid esters, the best Indexes of performance In the Number Facility Test under the Influence of such esters are the scores In the lie, l pochondrlasls, and mania scales of the MMPI. 

After a similar analysis for five anticholinergic compounds, three other substances trlth atropine and scopolamine, IClapper et al. (162) decided that scores In the positive test-taking attitude, hypochondriasis, and mania scales of the MMPI were positively related to performance In the Number Facility Test. 

Although the ratios between the ED qs of atropine and of the other anticholinergic compounds for the production of the different effects varied somewhat, intravenously injected scopolamine hydrobromide was about 8.7 times as active as atropine sulfate and, when Injected Intramuscularly, about 7.5 times as effective as atropine sulfate. Scopolamine methylbromlde was about A times as active as atropine sulfate, except chat no dose of the former substance produced as much as a 9CX decrease In performance In the Number Facility Test, so comparative potencies had to be assigned on the basis of less than maximal actions by atropine and scopolamine. Therefore, scopolamine methylbromlde was only about 532 as potent as the l dro bromide. 

Intramuscular injections of scopolamine hydrobromide at 26 pg/kg and of atropine sulfate at 175 ug/kg Induced approximately equal decrements In performance In the Number Facility Test, except that the maximal effect after scopolamine was attained in about half the time required to reach that after atropine. Intravenously Injected scopolamine hydrobromide produced Its maximal effect even more rapidly than that Injected Intramuscularly. Scopolamine mett lbromlde was slower In exerting Its maximal tachycardlsd. effect than scopolamine faydrobromlde, but no Information about the rapidity of Its action on performance In the Number Facility Test was provided In any of the three reports (24,165,166). The Increase In heart rate Induced by scopolamine methylbromlde was greater than those Induced by the same amounts of scopolamine hydrobromide or atropine sulfate. 

Kiczes and Vancll (230) reported the results of a study to determine the Intramuscular dose of 3-quinuclldii l benzllate that constitutes the minimal effective dose (MED) for a man, here defined as the smallest dose chat produces a decrease of at least 25% in performance in the Number Facility Test. The effects on heart race were also recorded. Thirteen male volunteers were given intramuscular injections of 3-qulnuclldlnyl benzllate hydrochloride at 2.3 or 2.7 pg/kg. 

One man given 2.7 pg/kg became confused and developed hallucinations. The most common complaints of the other volunteers were of dry mouth, blurred vision, and drowsiness Several developed restlessness, an inability to sleep despite drowsiness, and anorexia. Of six men given 2.3 pg/kg, one had a decrease in performance in the Number Facility Test of more than 252, and three had dilated pupils. This dose Induced no tachycardia or hyperthermia. Of seven men given 2.7 pg/kg, five had decreased performance in the Number Facility Ttest of more chan 25%, three had dilated pupils, two had heart rates greater than 100 beats/mln, and one had a blood pressure above 140/90. There were no cases of hyperthermia (the report did not state the environmental conditions of the study). The mean heart rate after the larger dose was about 92 beats/min, whereas that after the smaller dose was about 79 beats/min. 

Kiczes and Vancll estimated that the MED related to performance in the Number Facility Test was 2.54 pg/kg, with 95% confidence limits of 2.31 and 2.80 pg/kg, and chat the MED for inducing changes in somatic functions (vision, heart rate, and blood pressure) was about 2.7 pg/kg. 

Sldell et al. (164) found that -(2-dllsopropylamlnoethyl)-ec Q lmethylphosphonothloace Tnjected intravenously at 1.5-1.7 pg/kg after Intramuscular Injection of 3-qulnuclldlnyl benzllate at 6 pg/kg was effective In Inducing rapid Improvement In the scores of three volunteers in Che Number Facility Test. This finding was similar to that reported earlier in subjects exposed to scopolamine. 

Sldell (168) reported that four volunteer subjects given Intramuscular Injections of 3-qulnuclidlnyl benzllate at 7 ug/kg had their scores In tha Number Facility Test Improved dramatically by Intramuscular injection of 7 or 11 mg of physostlgmine salicylate followed by oral administrations of 24 or 12 mg, respectively, of the same drug during total periods of treatment of 43 and 42 h, respectively. Two other subjects given Che same dose of the benzllate were treated entirely with oral administration of physostlgmine in total doses of 80 and 211 mg during periods of treatment of 37 and 71 h, respectively, the scores In the Number Facility Test of the last two subjects were better maintained than those of the first two. 

Kltzes and Ketchum (237) reported giving 39 volunteers Intramuscular EA 3443 at 1.0-2.7 pg/kg. These doses Induced no hallucinations or abnormal neurologic signs. Dry mouth, blurred vision, and drowsiness were the most common complaints, t drlasls occurred to a mild degree. There was no consistent dose-response relationship for the heart rate, but that rate may have been decreased, rather than Increased. The minimal effective dose for reducing performance in the Number Facility Test of half the subjects by at least 25Z (HED5Q) in this study was 1.21 pg/kg, with 95% confidence limits of 1.00 and 1.48 pg/kg. The time for onset of these minimal effects was about 8 h, and the duration of effects was about 4 h. 

Kltzes et al. (154) found that 80Z of a group with a mean body weight of 87.2 kg who had been given EA 3443 at a mean dose of 2.2 pg/kg suffered degradation of their performances In the Number Facility Test. Only 46.7% of a group with a mean body weight of 71.6 kg who had received a mean dose of 2.4 Pg/kg suffered degradation of their performances In the same test. In the case of this compound, therefore, body size may have conditioned the response. 

Lavallee (50) reported that the minimal intravenous dose of EA 3443 that decreased performance by at least 25Z In the Number Facility Test by half the members of a group of volunteers was 1.2 pg/kg. The corresponding Incapacitating dose, the ID50, was 3.1 pg/kg. That for 3-qulnuclidlnyl benzllate was 6.6 pg/kg. When EA 3443 was Injected Intravenously into dogs trained In a multiple-stimulus conditioned—avoidance test, a dose of 100 pg/kg decreased the... 

Sldell and Braun (254) discussed the results of an experiment in which two men were given EA 3834 by mouth at 7 yg/kg, four were given 10 yg/kg, three were given 14 yg/kg, and two were given 20 yg/kg. One man given 7 yg/kg and two given 10 yg/kg suffered severe effects (reduction of score In the Number Facility Test to below 25% of the baseline score). All the men given 14 and 20 ug/kg experienced severe effects. 

Mild effects (reduction of score In the Number Facility Test by at least 25Z of the baseline score) for all the severely affected subjects lasted 10-14.5 h (mean, 11.2 h), whereas chose In the two men who took 10 ug/kg without developing severe effects lasted for 3 and 7.5 h. Mild effects In the two men given 10 ug/kg who never developed severe effects began 2.5 and 3 h after Ingestion. In the eight men who developed severe effects, the mean onset time for mild effects was 1.3 h (95Z confidence limits, 1.0 and 2.0 h). 

On the day of the test. Intramuscular Injections were given at 9 a.m., and the exercise was started Immediately. It ended at 4 p.m. A battery of tests (heart rate, blood pressure, rectal temperature. Number Facility Test, and behavioral checklist) was administered to each volunteer at 9 30, 10, and 11 a.m., noon, and 1 and 4 p.m. The performance of volunteers on this day was graded by the same Judges who had been present on the control day. 

Copelan (257) summarized experiments In which 20. volunteers were given 302,668 Intravenously at 1.0-. 6 pg/kg and were tested at Intervals for ability to perform In the Number Facility Test. Hen given doses of 1.0, 1.4, and 2.0 pg/kg lost less chan 25Z of their baseline abilities to perform the additions. Of four men given 2.7 ug/kg, two lost at least 2SZ of their abilities. Of four men given 3.2 ug/kg, one lost 29Z and another lost 24Z. Four men given 3.8 ug/kg and two given 4.6 ug/kg had mean decrements of 41Z and 50Z, respectively, and all lost at least 25Z of their abilities. 

Karger (258) estimated the ID50 of 302,668 by giving 14 volunteers Intravenous doses of 5.0 11.0 ug/kg and administering the Number Facility Test at Intervals thereafter. Incapacitation was defined as the making of two consecutive scores below lOZ of the baseline score. A clinical evaluation of incapacitation based on observation of the subjects was also made. Xbc scores on the Number Facility Test yielded an IO50 of 10.1 ug/kg, with 95Z confidence limits of 9.2 and 11.1 ug/kg. The clinical evaluations yielded an estimated IO5Q of 9.5 ug/kg, with 9SZ confidence limits of 8.5 and 10.6 ug/kg. 

As a second pare of the same study, Karger gave six volunteers 302,668 intravenously at 10 ug/kg and administered physostlgmine at various times. An Intramuscular dose of 3 mg of ph/soselgiBlne Injected 10 isln before administration of 302,668 attenuated the decrement In performance In the Number Facility Test for about 4.S h after Injection. At that time the performance of two unprotected subjects and of the two prophylactlcally protected subjects became essentially Identical. When a dose of 3 mg of physostlgmine was Injected Intramuscularly 10 min after Intravenous Injection of 302,666, there was rapid recovery from about 35Z of baseline performance to about 92Z, but performance In the Number Facility Test was down to about 20Z of baseline by 2 h after the Injection of 302,668. When the pt sostlgmlne was not Injected until 45 min after the agent, performance in the Number Facility Test rose from zero to about 85Z within about 45 min and to a peak of... 

Lavallee (50) collected and graphed data from human experiments that Indicated that 302.668 at comparatively low doses (below 4 ug/fcg) approached 3-qulnuclldli l benzllate in activity In decreasing performance In the Number Facility Test, but at higher doses (above 9 ng/kg) was only slightly more active than scopolamine Extrapolation of Lavallee s graphs suggests chat the doses of 302.668 and of scopolamine that would be able to lower performance in the Number Facility Test to zero would be Identical. 

Lavallee (50) collected data froa studies of the effects of 302,196 on huaan subjects that enabled him to draw a line relating the effects on the score In the Number Facility Test to the logarithm of the dose. This ester was less effective than scopolamine In decreasing the ability to perform this test. 

Kltzes aJ (154) found that two groups of men with average body weights of 83 1 and 66.7 kg that had received similar doses of EA 3580 (3.1 and 3 2 ng/kg, respectively) suffered significant decrements In their scores In the Number Facility Test In 45.5Z and 53.8Z of the cases, respectively. 

Klapper e a. (163) found that, for six men given a mean EA 3580 dose of 1.8 >ig/kg by Intramuscular Injection, the scale of the MMPI yielding the greatest correlation with their performances In the Number Facility Test was chat for hysteria. For seven men given a mean dose of 3.5 ug/kg, the scale with the best correlation was that for mania. For the lower dose, the most negative correlation was with the paranoia scale for the larger dose, the most negative correlation was with the depression scale. 

Sldell et al. (164) found that Intravenous Injection of -(dllsopropylamlnoetbyl)-etliylmethylphosphonothloace Into men Intoxicated with sufficient EA 3580 to decrease performance In the Number Facility Test to 15Z or less of their baseline values removed the decreases promptly and nearly completely. Oral administration of the same phosphonothloate was ineffective. The doses of the theraupetlc compound were not stated oral administration of a different dose of the phosphonothloate might be effective. 

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