The Effect of Varying Oral Dosages of Banthine, Probanthine and Prantal on the Galvanic Skin Response
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View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector THE EFFECT OF VARYING ORAL DOSAGES OF BANTHINE, PRO- BANTHINE AND PRANTAL ON THE GALVANIC SKIN RESPONSE* DANIEL J. PERRY, M.D.,t GEORGE E. MOUNT, Pu.D.t AND BOYD W. BROWNE, B.A.* Recent experiments have demonstrated the effects on the Galvanic Skin Resistance (GSR) of certain drugs which either stimulate or suppress sweat gland activity (1, 2). In a study of sympathectomized subjects, evidence has been pre- sented which substantiates the theory that the GSR phenomenon is related to sweat gland activity (3). Significant differences between placebo, atropine and pilocarpine have also been found regardless of the order of administration (4). In addition, repeated placebo injections have indicated that no significant adapta- tion occurred (4). The results of the above investigations have suggested the possibility of using the GSR to compare the dose-response effects of certain drugs. Therefore, the present study was initiated to evaluate varying oral dosages of Banthine (methan- theline bromide), Pro-B anthine (propantheline bromide), Prantal (diphemanil methylsulfate) and placebo. MATERIALS AND METHODS The subjects for the present experiments were ten normal white males ranging in age from 19 to 33 years. Each individual was tested separately to 50 and 100 mgm. of Banthiiie, 15 and 30 mgm. of Pro-Banthine, 100 and 200 mgm. of Pran- tal and a placebo. The order of drug administration was varied in each subject to obtain an approximate representation of the total iiumber of possible orders. All tests were made in the morning after breakfast and completed before lunch. Following the oral administration of the test drug, the GSR was recorded for 90 minutes on a Esterline Angus milliameter using a previously reported technic (1, 2). The chart record for each test consisted of 24 periods of 3 minutes. Instrument calibrations were made preceding, at the middle and at the end of each experiment. RESULTS The high and low resistance levels for each 3 3, minute period were determined by linear interpolation between the calibrations for each record. These values were then converted intoV'micromhos using the formula (1/R.106)t. The data for all subjects were averaged separately for each of the seven experimental conditions and preliminary curves plotted as shown in Figure 1. These results *Fromthe Division of Dermatology,t Department of Medicine, University of California, the Departments of Psycho1ogy and Engineering, University of California, Los Angeles, California and the Medical Service, Veterans Administration Center, General Medical and Surgical Hospital, Los Angeles, California. This study was aided by a grant from the G. D. Searle and Co., Chicago, Illinois. Received for publication July 23, 1956. 239 240 THEJOURNAL OF INVESTIGATIVE DERMATOLOGY EFFECT OF DRUGS ON GSR LEVEL UNCORRECTED CURVES 3.5 IC1(0 1:0 10 10 'U 00 mg.Banthine 50 — 30 Pro-Banthine 15 200 Prantal 00 Placebo 0 0 20 30 40 50 60 70 80 90 MINUTES FROM POINT OF ADMINISTRATION FIG. 1. Effect of drugs on GSR level (uncorrected curves) TABLE 1 Regression coefficients on initial levels Time Period Drug 3 12 24 Placebo 0.9 0.9 0.8 Pro-Banthine, 15 mgm 1.0 0.8 0.7 Pro-Banthine,3omgm 1.0 0.8 0.6 Banthine, 50 mgm 0.9 0.6 0.5 Banthine, 100 mgm 0.8 0.5 0.5 Prantal, 100 mgm 1.0 0.7 0.7 Prantal, 200 mgm 0.8 0.7 0.7 Mean 0.9 0.7 0.6 Correction 0.8 0.5 0.5 demonstrate some variation in the initial levels for the different experimental con- ditions and indicate the possibility of correcting the curves for these initial dif- ferences. Values for each subject for each drug at the third, twelfth and twenty-fourth time periods were used in the correction. The relation of these values to the initial levels was determined separately for each drug and used to correct the obtained curves. This was done by computing the regression coefficients of the values at each of the time periods on the initial levels for each drug condition (5). Table I GALVANIC SKIN RESPONSE 241 showsthe results of these Computations and the correction Values which were used. The correction for intermediate time periods was based on a linear inter- polation of the correction values shown in Table 1. The transformation which has been outlined is analogous to that on which the statistical analysis of covariation is based. The maj or assumptions are that the true regression is approximately linear, that the same regression slope approxi- mately applies to each of the conditions for which a correction is made and that the obtained values are approximately representative of the true values. The applicability of the transformation for the correction of the initially obtained curves is supported by the similarity of the results obtained for each experimental condition. The importance of the assumptions is minimized by choosing conserva- tive values for the correction (i.e. values that modify the curves toward, but which probably fall slightly short of the true curves). Thus, in the event that an error occurs, it is more likely that the correction is in the right direction, hut slightly less than would have been made if the true regression values could be known. DIscussIoN Figure 2 shows that the curves for the placebo, 100 and 200 mgm. Frantal and 15 and 30 mgm. Pro-Banthine follow a similar course. At the end of the experi- ment there tends to be some differentiation between the drugs and placebo. How- ever the differences between these four drug dosages and the control are not sig- nificant at the 5 % level of confidence. The differences between drugs and placebo do occur in the direction which would be anticipated from previous experiments EFFECT OF DRUGS ON GSR LEVEL 4.0F CORRECTED CURVES 101w It2 IC I2: jO t 00mg. Banthine 50 15 200 Prantal 100• MINUTES FROM POINT OF ADMINISTRATION FIG. 2. Effect of drugs on GSR level (corrected curves) 242 JOURNAL OF INVESTIGATIVE DERMATOLOGY (1, 4) in which atropine, Banthine and Pro-Banthine consistently had a lower GSR level (increased resistance or decreased sweating) than the control. In the present study we again see this trend. Furthermore, the 200 mgm. Prantal and 30 mgm. Pro-Banthine dosages seem to produce lower GSR levels than the 100 and 15 mgm. dosages of the corresponding drugs. This suggests that dose-response ef- fects of varying dosages of anticholinergic drugs can be compared using the present technic. Figure 2 shows that both 50 and 100 mgm. of Banthine were followed by pro- gressively decreasing GSR levels as contrasted with the other drugs and control. The differences between each dose and the control are statistically significant beyond the 1 % level of confidence. Also, 100 mgm. Banthine produces a lower GSR level than 50 mgm. However, both the 50 and 100 mgm. dosages produces more effect than either dose of Pro-Banthine or Prantal. CONCLUSIONS 1. The GSR level as described in these experiments can be used to evaluate the dose-response effects of varying oral dosages of anticholinergic drugs. 2. Orally administered Banthine appears to have a greater effect on the GSR level than Pro-Banthine or Prantal in the dosages used in the present experi- ments. REFERENCES 1. PERRY, D. J. AND MOUNT, G. E.: A comparison of the effect of atropine and placebo on the galvanic skin resistance. J. Invest. Dermat., 22: 497—501, 1954. 2. PERRY, D. J., MOUNT, G. E. AND HULL, C. D.: Effect of drugs on galvanic skin resistance (Comparison of methantheline, propantheline and a placebo). Arch. Dermat. & Syph., 71: 476—477, 1955. 3. PERRY, D. J. AND MOUNT, G. E.: Effect of drugs on galvanic skin response level. A study in sympathectomized human subjects. Arch. Dermat. & Syph., 72:144—152,1955. 4. PERRY, D. J., MOUNT, G. E., HULL, C. D. AND ZEILENGA, R. H.: Effect of order of drug administration on the galvanic skin resistance in human subjects. J. Invest. Dermat., 25: 179—185, 1955. 5. GUILFORD, J. P.: Fundamental Statistics in Psychology and Education, pp. 211—214. New York, McGraw-Hill, 1942..