A. Morphine
Synonyms Morphium; Morphia; Dolcontin; Duromorph; Morphina; Nepenthe.
Biological Sources Morphine is obtained from a variety of medicinal plants, such as: Argemone mexicana L. (Papaveraceae) (Prickly Poppy); Eschscholzia californica Cham. (Papaveraceae) (California Poppy); Papaver bracteatum Lindl. (Papaveraceae) (Great Scarlet Poppy; Thebaine Poppy); Papaver somniferum L. (Papaveraceae) (Opium Poppy; and Poppyseed Poppy Keshi).
Chemical Structure
(5α, 6α)-7, 8-Didehydro-4, 5-epoxy-17-methylmorphinan-3, 6-diol; (C17H19NO3).
Isolation The latex obtained by incision on the unripe capsule of opium poppy is first collected in clean, plastic containers, and the process of incision is repeated at least four times on the same capsule after an interval of two days. Care must be taken to make the incisions on the superficial surface only so as to collect exclusively the external exudation of latex. Subsequently, the latex is dried carefully either by exposing to air on metallic shallow plates or by passing a stream of hot air.
Thus the ‘opium’ or the dried latex is stored for the isolation of morphine. It is found to contain usually 9.5% morphine when calculated as anhydrous morphine.
The morphine may be isolated form ‘Powdered Opium’ by adopting the following steps sequentially:
Step-1: The powdered opium is shaken with calcium chloride solution and filtered.
Step-2: The resulting filtrate is concentrated and to it is added 10% w/v sodium hydroxide solution carefully i.e., to solubilize morphine, codeine and narceine. It is now filtered.
Step-3: The filtrate containing morphine, codeine and narceine is extracted with chloroform. The resulting mixture is separated.
Step-4: The lower chloroform layer contains codeine, whereas the upper aqueous layer comprises of morphine and narceine.
Step-5: The aqueous layer is first acidified and subsequently made alkaline with ammonia, whereby morphine gets precipitated and collected as a while solid residue (Yield = 9.5%).
Characteristic Features
1. Morphine is obtained as short, orthorhombic, columnar prisms from anisole that gets decomposed at 254°C. It also occurs in its metastable phase having mp 197°C. However, the high melting form sublimes at 190-200°C (0.2 mm pressure at 2 mm distance).
2. It has a bitter taste.
3. Morphine (free-base) unlike most other alkaloids in their free-base forms is found to be sparingly soluble in chloroform and nearly insoluble in ether or benzene.
4. Morphine gets dissolved in caustic alkalies by virtue of the fact that the OH moiety at C-3 is phenolic in nature and the other OH function at C-6 is a secondary alcoholic group.
5. Morphine is a monoacidic base and hence, forms salts that crystallizes rapidly. These are found to be neutral to litmus and methyl orange.
6. The average pH of a saturated solution of morphine salt is found to be 4.68.
Note: Morphine reduces iodic acid and potassium iodate.
4. Sodium Nitrite Test: To a solution of morphine in dilute HCl add a few drops of sodium nitrite solution (1% w/v). Allow the reaction mixture to stand for 5-8 minutes and then make it alkaline with dilute ammonia solution, the development of a red colour confirms the presence of morphine.
Note: (1) It is a non-specific test for morphine and is also given by other phenolic substances.
(2) It legitimately distinguishes morphine from codeine.
5. Nitric Acid Test: Morphine readily gives an orange-red colouration when a few mg of it is treated with a few drops of concentrated nitric acid.
(a) The resulting orange-red colouration rapidly changes to yellow on heating.
(b) The orange-red colouration gets easily disappeared on the addition of a few drops of stannous chloride solution (SnCl2) (1% w/v).
6. Ferric Chloride Test: When a neutral solution of morphine is treated with a few drops of ferric-chloride solution (1% w/v), a greenish-blue colour is produced.
Derivatives of Morphine A number of derivatives of morphine are produced that essentially have distinct characteristic features as enumerated below:
1. Morphine Monohydrate (C17H19NO3.H2O):
(i) It is obtained as orthorhombic, sphenoidal prisms, or needles from methanol that gets decomposed at 254-256°C with rapid heating.
(ii) It darkens on exposure to light and also loses water of crystallization at 130°C.
(iii) Its physical parameters are: dD20 1.32; [α]D25 -1320(methanol); pKb at 20°C = 6.13, pKa 9.85; pH of a saturated solution 8.5; and uvmax in acid: 2.85 nm, in alkali: 298 nm.
(iv) Solubility Profile: 1 g dissolves in about 5000 ml of water, 1100 of boiling water, 210 ml of ethanol, 98 ml of boiling ethanol, 1220 ml of chloroform, 6250 ml of ether, 114 ml of amyl alcohol, 10 ml of boiling methanol, 525 ml of ethyl acetate; freely soluble in solutions of fixed alkali and other alkaline earth hydroxides, in phenols, cresols; moderately soluble in mixtures of chloroform with alcohols; and slightly soluble in ammonia benzene.
2. Morphine Acetate Trihydrate (C19H23NO5.3H2O):
(i) It is a yellowish-white powder.
(ii) It has a slight acetic odour.
(iii) It specific optical rotation [α]D15 -770 (water).
(iv) It dissolves 1 g in 2.25 ml of water, 2 ml of boiling water, 22 ml of ethanol, 2 ml of ethanol at 60°C, 4.5 ml of glycerol, 4.75 ml of chloroform; and practically insoluble in ether.
3. Morphine Tartrate Tihydrate [(C17H19NO3)2.C4H6O6.3H2O)]: It is obtained as a crystalline powder. It is soluble in 11 parts of water; slightly soluble in alcohol; and practically insoluble in ether, chloroform and carbon disulphide.
Uses
1. It is used as a potent narcotic analgesic.
2. It is usually given in severe pains and also in such instances where patient fails to show positive response to other analgesics.
3. It exerts a biphasic action on the CNS.
4. It is found to sedate the respiratory centre, emetic centre and the cough centre through its action in the medulla.
5. It stimulates the chemoreceptor-trigger-zone located in the medulla that ultimately causes nausea and vomilting; and this is perhaps regarded as a side-effect.
6. It also exerts sedative and hypnotic actions.
Note: Morphine and its salts are habit forming drugs. Hence, its use must be done under the strict observation of a physician.
