ELECTROCHEMICAL AND PHARMACOLOGICAL ANALYSIS OF CU-ATROPINE COMPLEX

ELECTROCHEMICAL AND PHARMACOLOGICAL ANALYSIS OF CU-ATROPINE COMPLEX

Rakesh Choure * and S. K. Abdus Samim

Department of Chemistry, Government SSP College Waraseoni, Balaghat, Madhya Pradesh, India.

ABSTRACT: The Cu-Atropine complex may have potential applications in medicinal chemistry, as atropine is used in the treatment of certain medical conditions such as bradycardia and as a pre-anesthetic to decrease salivation. Additionally, the complexation of atropine with copper could potentially enhance its therapeutic effects or alter its pharmacokinetic properties. In the present study, the drug has been modified by complex formation with absolute methanol and concentrated sulphuric acid following standard procedures to increase its potency. IR spectra of Cu- atropine complex has taken. The analytical data indicates that a complex form of the drug, Cu-Atropine, is formed in a 1:1 ratio. To study the interaction between drugs and metal complexes, differential pulse polarography (DPP) has been used. These techniques are simple and cost-effective, making them suitable for qualitative and quantitative determination of active drug compounds. In a pharmacological study, modified atropine showed more potency compared to its parent drug.

Keywords: Atropine, DCP, DPP, Anesthetic drug, In-vivo study

INTRODUCTION: In the modern age, an analytical chemists solve their chemical analysis problems quantitatively and qualitatively by making use of some instrumentation techniques, like polarography, pH metering, spectroscopy etc. Past three decades have witnessed a wider use of electroanalytical techniques for the study of metal complexes in solution. For metal ligand system it is possible to determine the degree of formation, distribution and stability constants of all species present.

Polarography, finds an extensive use in the determination of various organic and inorganic depolarizers present even in micro to ultra micro quantity. For a current voltage curve, if the specific rate of the electrochemical reaction is very high, so that the current is controlled essentially by diffusion process, the calculation of the shape of the current-voltage curves is relatively very easy and such process is termed as the reversible electrode process.

In the last two-three decades, the technique has found increasing application as a means of identifying the stoichiometry and formation constants of coordination compounds. Looking at the usefulness of polarographic methods in the analysis of organic compounds, it has been used to study the chemistry of atropine (in the study of adsorption, complex formation, inhibition of chain oxidations, and the mechanism of organic reactions).

EXPERIMENTAL: All the chemicals used were of Himedia/BDH/CDH grade. The sulphate of Cu²⁺ was used. Double distilled water was used to prepare all the solutions. Stock solution of 1M Borate buffer and .01M Atropine was prepared in double distilled water and alcohol.

Experimental sets were prepared by keeping overall metal ion and supporting electrolyte (borate buffer) concentrations fixed at 1.0mM and 1.0M respectively. The pH of the solution was adjusted to 8.2 ±0.1. The necessary amount of boric acid and sodium Hydroxide solution was used to adjust the pH of test solutions. The experimental set was prepared by taking 1ml of sample solution and 10ml of borate buffer as supporting electrolyte in a polarographic cell and the total volume was made is 50ml with distilled water. The pH of the test solution was adjusted to 8.2±0.1.

RESULTS AND DISCUSSION: Atropine and its complexes gave well-defined cathodic reduction wave at pH = 8.2±0.1 in 1M Borate buffer. The plots of i_d vs √h_corr yielded straight lines in each case, passing through the origin confirming the diffusion controlled nature of the reduction process.

Effect of Ligand Concentration:-On increasing the ligand concentration in each set and subjecting these experimental set to polarography. It was observed that the half wave potential shifted to more electronegative value. The plot of change in half wave potential with logarithm of change in ligand concentration yielded a straight line, suggesting the formation of single complex species in case of Cu(II)-Atropine system, Fig. 2. Lingane’s treatment of the observed polarographic data in case of Cu(II)-Atropine system, revealed the stoichiometry and formation constants of the complexes formed. The results have been tabulated Table 1.

TABLE 1: FORMATION CONSTANTS OF ATROPINE COMPLEXES

TABLE 2: POLAROGRAPHIC DATA ON CU(II) – ATROPINE COMPLEX SYSTEM. Cu(II)=1.0 mM, 1.0 M Borate buffer pH = 8.2±0.1,

log β₁= 8.40

Polarograms of Cu(II)-Atropine Complex:

FIG. 1A: DIRECT CURRENT POLAROGRAM OF Cu(II)-ATROPINE COMPLEX IN BORATE BUFFER (0.2M) AT pH 8.2±0.1.

FIG. 1B: DIFFERENTIAL PULSE POLAROGRAM OF CU(II)- ATROPINE COMPLEX IN BORATE BUFFER (0.2M) AT pH 8.2±0.1.

Plot of E_1/2 vs log Cx:

FIG. 2: CU(II)-ATROPINE COMPLEX

IR Spectral Analysis of Cu(II)-Atropine Complex: On comparing the IR spectra of atropine and its Cu(II) complex, it was observe that the band at 1730 cm^-1 due to C=O group in the spectrum of pure drug disappeared in the spectrum of its Cu(II) complex and also the sharp –OH signal at 3608 cm^-1 observed in atropine is shifted to  3650 cm^-1 in the spectrum of Cu(II)-atropine complex, which confirms involvement of C=O and –OH in the complexation of the drug with Cu(II). Thus on the basis of polarographic and IR studies a tentative structure to 1:1, Cu(II)-atropine complex may be as under.

FIG. 3: IR SPECTRA OF CU- ATROPINE COMPLEX

Pharmacological Experiments: A rabbit was placed in a Rabbit holder (box) keeping the head out side. The size of the rabbit pupil of both eyes was observed. The effect of light reflex of the rabbit’s eye to and fro was observed. The corneal reflex was examined by touching a side of the cornea with a cotton piece. A few drops of atropine were instilled in the conjunctiva (4-6 times) over a period of 8-10 minutes in the right eye of the rabbit. The left eye of the rabbit served as control. The pupillary size was recorded after 10 minutes of drug instillation and the data was tabulated. The experiment was repeated with atropine complexes. Table 3 shows that Cu(II)-Atropine complex is more potency anesthetic drug of the two complexes under study.

TABLE 3: EFFECT OF ATROPINE AND ITS COMPLEXES CU (II) INSTILLATION ON THE PUPILLARY SIZE OF EXPERIMENTAL RABBIT

CONCLUSION: The observed analytical data clearly speaks the formation of complex form of the drug (Cu-Atropine) in 1:1 ratio in each case.

Results of pharmacological study on the anesthetic activities of above systems showed that the modified drug complex is found to be more potent than parent atropine drug.

On the basis of reported data and ongoing discussion it could be concluded that the proposed electroanalytical methods provide accurate and precise data on trace analysis of atropine and its modified forms. The techniques are best suited because of simplicity as well as economics of the procedure for the simultaneous qualitative and quantitative determination of traces of active principles of drugs and may be recommended for their possible use in medicinal industries. The author also recommends the modified drugs to the therapeutic experts to ascertain the possible use of the modified forms as more potent anesthetics in lieu of parent atropine drug.

ACKNOWLEDGEMENT: The author is grateful to Dept. of Chemistry, Government SSP College Waraseoni for support and thankful to S. K. Abdus Sami for his advice and encouragement throughout preparation of the manuscript.

CONFLICTS OF INTEREST: The authors declare that there are no conflicts of interest.

REFERENCES:

1. Weinberg GL, Ramaraju GA, Garcia-Amaro MF and Cwik MJ: Pretreatment or resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced a systole in rats. Anesthesiology 1998; 88: 1071-5.
2. Weinberg G, Ripper R, Feinstein DL and Hoffman W: Lipid emulsion infusion rescues dogs from bupivacaine-induced cardiac toxicity, Regional Anesthesia and Pain Medicine 2003; 28: 198-202.
3. Picard J and Meek T: “Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob. Anesthesia 2006; 61: 107-9.
4. Rosenblatt MA, Abel M, Fischer GW, Itzkovich CJ and Eisenkraft JB: Successful Use of a 20% lipid emulsion to resuscitate a patient after a presumed bupivacaine-related cardiac arrest. Anesthesiology 2006; 105: 217-8.
5. 5Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): May 17, 2021. Belladonna.
6. Rang HP, Dale MM, Ritter JM and Flower RJ: Rang and Dale's Pharmacology. Elsevier Churchill Livingstone 2007; 153.
7. Robert S and Holzman MD: The Legacy of Atropos". Anesthesiology 2007; 89(1): 241–249.
8. Arthurs AJ and Davies R: Atropine - a safe drug. Anesthesia 1980; 35: 1077-1079.
9. Gilman AG, Goodman LS, Rall TW, Murad F and Weiner N: Atropine, scopolamine, and related antimuscarinic drugs. In The Pharmacological Basis of Therapeutics 7th ed. MacMillan, New York 1985; 130-138.
10. Lullmann H, Schmaus H, Staemmler E and Ziegler A: Comparison of atropine and dexetimide in treatment of intoxications by selected organophosphates Acta Pharmacol et Toxicol 1982; 50: 230-237.
11. McEvoy G: Anticholinergic agents”, AHFS drug information, American Hospital Formulary Service, Bethesda 2002; 1222-1228.
12. Berghem L, Bergman U and Schildt B: Plasma atropine concentrations determined by radioimmunoassay after single-dose iv and im administration”. Br J Anaesth 1980; 52: 597-601.
13. Finar IL: Organic Chemistry, Vol. 2 4th. Edn, Longman, 1965; 631–639.
14. Scully C, Limeres J, Gleeson M, Tomás I and Diz P. J: Oral Pathol Med 2009; 38: 321–327.
15. Squires N, Wills A and Rowson J: The management of drooling in adults with neurological conditions. Curr Opin Otolaryngol Head Neck Surg 2012; 20(3): 171-6.
16. Wecker, Lynn, Dettbarn, Wolf-D, Schmidt and Dennis E: Choline Administration: Modification of the Central Actions of Atropine”, Science 2000; 199(4324): 86-87.
17. Monteiro R, Daniela, Campagnol, Letícia, Parrilha R and Luísa and Furlan Z: Evaluation of cardiorespiratory effects of combinations of dexmedetomidine and atropine in cats, Journal of Feline Medicine & Surgery 2009; 11: 783-792.
18. Krzyzak M, Regina A, Jesin RC, Deeb L, Steinberg E and Majlesi N: Anticholinergic Toxicity Secondary to Overuse of Topricin Cream, a Homeopathic Medication. Cureus 2018; 10(3): 2273.
19. Ho ML, Gatien M, Vaillancourt C, Whitham V and Stiell IG: Utility of prehospital electrocardiogram characteristics as prognostic markers in out-of-hospital pulseless electrical activity arrests. Emerg Med J 2018; 35(2): 89-95.
20. Portillo R, Sanz-Pedrero P and Bashuelves F: Polarographic determination of alkaloids. I. Polarographic Behavior of Atropine 1955; 21(1): 37-42.
21. Drugs and Lactation Database (LactMed®) [Internet]. National Institute of Child Health and Human Development; Bethesda (MD): Feb 15, 2021. Atropine.
22. Wu PC, Chuang MN, Choi J, Chen H, Wu G and Ohno-Matsui K: Update in myopia and treatment strategy of atropine use in myopia control. Eye (Lond) 2019; 33: 3–13.
23. Avetisov SE, Fisenko VP, Zhuravlev AS and Avetisov KS: Atropine use for the prevention of myopia progression. Vestn Oftalmol 2018; 134(4): 84-90.
24. Latifa, Rabi, Adnane, Moutaouakkil, Mohamed and Blaghen: Ionophoric properties of atropine: complexation and transport of Na +, K +, Mg2+ and Ca2+ ions across a liquid membrane: Natural Product Research: Formerly Natural Product Letters 2008; 1478-6427, 22(6), 547–553.
25. Terufumi F, Ujiwara, Imdad U, Mohammadzai, Katsumi, Murayama and Takahiro Kumamaru: Solvent Extraction Coupled On-Line to a Reversed Micellar Mediated Chemiluminescence Detection System for Trace-Level Determination of Atropine. Anal Chem 2000; 72(7): 1715–1719.
26. Ryang S, Takei S, Kawai T, Imaizumi Y and Watanabe M: Atropine-resistant relaxation induced by high K+ in iris dilator muscle of the rat and pig 2000; 86-87.
27. Seo KY, KimM CY, Lee JH, Lee JB and Kim EK: Amniotic membrane transplantation for necrotising conjunctival ulceration following subconjunctival atropine injection. Br J Ophthalmol 2002, 86: 1316-1317.
    

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    How to cite this article:

    Choure R and Samim SKA: Electrochemical and pharmacological analysis of cu-atropine complex. Int J Pharm Sci & Res 2024; 15(3): 808-12. doi: 10.13040/IJPSR.0975-8232.15(3).808-12.

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