Papaverine, an opium constituent, has antispasmotic properties and has
also been used as an analgesic. Today it is used as a minor constituent
with morphine usually to enhance the analgesic properties of a weaker drug
such as aspirin.
Emetine is a derivative of tetrahydro isoquinoline which is isolated from the root of a S. African creeper. It has been used as an expectorant, but now replaced by codeine and other non alkaloid drugs such as ephedrine and diphenylhydramine.
The most widely used of the quinoline alkaloids is quinine which is isolated from the bark of the cinchona tree. It is used as an antimalarial drug in 0.6 g doses, as a skeletal muscle relaxant it is used in .2 g doses to relieve nocturnal cramps and at trace levels as a bitter flavouring in tonic water.
3. Polycyclic alkaloids
The indole structure is also a common feature of alkaloid structures and can be identified as part of polycyclic alkaloids such as reserpine, vinblastine, strychnine and lysergic acid.
Of these reserpine has the most important clinical use i.e. for the
treatment of high blood pressure and as a tranquilliser.
Vinoblastine and its analogues are used to treat acute leukaemia, lymphomas and some solid breast and lung tumours.
Strychnine is very poisonous and was once used to control rodents, but it has been replaced by poisons which are less toxic to man.
The active ingredient of the ergot fungus which grows on cereal grasses such as rye, is a lysergic acid amide. LSD is the diethylamide derivative (X = NEt2) of lysergic acid has hallucinogenic properties. It has no medical applications, but ergotamine tartrate (a tripeptide derivative) is used to treat acute migraine. Its dihydro derivative is even more powerful.
Note that Cannabis (marijuana/Indian hemp), which is a mild hallucinogen, is a pyrone dreivative and not an alkaloid. It is also said to be "habit forming"
Morphine, which constitutes ca 10% of the extract from opium poppies,
is one of the most potent alkaloids. It is a very effective pain
killer and is used in medicine when pain is absolutely intolerable.
On the other hand, its acetyl derivative, heroin, is widely abused because of its short-term production of an overwhelming relaxing well-being feeling. Both are highly addictive and with prolonged use produce very harmful physiological effects on the body.
The most commonly used of this class of opioids in medicine is codeine.
It is a minor constituent of opium but is made by the methylation of morphine.
It is a fairly good analgesic but causes constipation. Thus about
8 mg is often added to either .4 or .5 g. tablets of aspirin or paracetamol.
It is also used as a cough suppressant and as an antidiarrhoeal drug.
It must be used with care since it is still addictive
although to a lesser extent than morphine.
Labelling work on a number of alkaloids has indicated that diaminocarboxylic acids are the main biochemical precursors of alkaloids.
Biosynthesis. - 1) Atropine. Feeding the Belladonna plant with the aminoacid ornithine which was 14C labelled at the C-2 position produced atropine labelled at the C-1 position as shown.
2) Nicotine. Feeding the tobacco plant with 14C-1 labelled aminoacid ornithine gave nicotine equally labelled at C-2’ and C-5’ sites as shown.
This indicated an intermediate in the biosynthetic
pathway which had a symmetrical distribution of the label such as 1,4-diaminobutane,
which could arise from decarboxylation of onithine. Feeding with
14C-2 15N-5 labelled ornithine gave nicotine with
50% loss on the 15N label whereas feeding with 14C-2
15N-2 labelled ornithine gave nicotine with 100% loss on the
15N label. These observations were attributed to
the presence of an equilibrium with the a-keto
3) Coniine. - Lysine was thought to be the most
likely precursor and indeed feeding the hemlock plant with 14C
labelled lysine produced radiolabelled coniine but the site of the label
was not investigated. However it was realised that lysine might be
degraded to a simpler compound which is the real precursor. Indeed
feeding the hemlock plant with diamino pentane and also with labelled acetate
also led to incorporation of the label. In addition feeding
of labelled acetate produces coniine with alternating carbon atoms (2,
4, 6, and 2’). labelled. It was concluded at this point that the
high level of label incorporation indicates that the actual biosynthesis
of coniine originates from a polyketide. Further work has indicated that
lysine is an intermediate but that it has the polyketide origin.
4) Lycopodine. Extensive studies of this alkaloid using 14C and 3H labelling has provided evidence that lysine is the starting material. This time 1,5-diaminopentane is the symmetrical intermediate. After oxidation it cyclises to form an imine which after addition of 2-propanone gives iso-pelletierine. Aldol condensation of iso-pelletierine followed by several more steps produces lycopodine with 25% of the 14C label spread amongst the carbonyl group and the 3 carbons bound.