Methyl Dopa2

8/3/2019 Methyl Dopa2

http://slidepdf.com/reader/full/methyl-dopa2 1/4

METHYL DOPA

Structure:

IUPAC Name: (S )-2-amino-3-(3,4-dihydroxyphenyl)-2-methyl-propanoic acid

Physico-chemical properties:

Molecular Weight 211.21452 [g/mol]

Molecular Formula C10H13NO4State Solid

Melting point 300OC

LogP -1.7H-Bond Donor 4

H-Bond Acceptor 5

Rotatable Bond Count 4

Solubility 1000 mg/L(1mg/ml) in water.Slightly soluble in water and alcohol; practically

insoluble in chloroform and ether; dissolves indilute mineral acids. Practically insoluble in the

common organic solvents.

Shelf-life of the substance 4 years.

Storage conditions Store in well-closed containers, at temperatures below 30°CProtect from light, keep dry.

Pharmacokinetic Parameters:

Pharmacokinetic data

Bioavailability approximately 50%

Metabolism Hepatic

Half-life 105 minutes

Excretion Renal for metabolites

Volume of Distribution 0.4 l/kg

Plasma protein binding Minimal

Barriers Crosses placenta, BBB

Renal clearance 130ml/min(healthy)



Mechanism of Action:

Methyldopa is a centrally acting antihypertensive agent. It is metabolized to alpha-

methylnorepinephrine in the brain, and this compound is thought to activate central

alpha-2 adrenergic receptors (Gerber, 1990).

Methyldopa has no direct effect on cardiac function and usually does not reduce

glomerular filtration rate, renalblood flow, or filtration fraction.

Methyldopa reduces vascular resistance. The fall in arterial pressure is maximal 6 to 8

hours after an oral dose.

Identification tests:

A: To about 10mg of finely ground tablets add 3 drops of ninhydrin in sulphuric acid (1in 250); a dark purple color is produced within 5-10minutes. Add 3 drops of water: thecolor changes to pale brownish yellow.

B: To about 10mg of finely ground tablets add 2ml of 0.1N sulphuric acid and 2ml of Ferrous tartarate solution prepared, then add 0.25ml of 6N ammonium hydroxide, and

mix; a dark purple color is produced immediately.

Dissolution:

Medium: 0.1N HCL; 900ml

Type 2 apparatus at 50rpm for 20minutes.

Tolerances- NLT 80% of the labeled amount dissolved in 20min.

Interactions:

1. Hypotension can be increased by concurrent administration of diuretics, other

antihypertensive agents, and general anaesthetics

2. Concomitant use of methyldopa and digoxin may produce symptomatic sinus

bradycardia.

3. Methyldopa and levodopa may enhance each other's therapeutic or adverseeffects. but it has also been claimed that methyldopa may inhibit the therapeutic

response to levodopa.

4. Concomitant use of methyldopa and lithium carbonate appeared to induce signs of lithium toxicity.

5. The action of methyldopa may be decreased by simultaneous use of non-steroidalanti-inflammatory agents.



6. CNS depressants including alcohol and narcotic analgesics, potentiate the

hypotensive action of methyldopa to a dangerous degree. When methyldopa is

administered with sedatives,hypnotics, tranquilizers, or other central nervoussystem depressants, further central nervous system depression may occur.

7. The hypotensive action of methyldopa may be inhibited by

amphetamines&sympathomimetic drugs, monoaminoxidase inhibitors, andtricyclic antidepressants.

8. Methyldopa may increase the hypoglycaemic effects of tolbutamide.

9. Methyldopa may increase prothrombin time if added to treatment with

anticoagulants.

10. Methyldopa may decrease the effect of ephedrine, since it reduces the quantity of

norepinephrine in sympathetic nerve endings.

11. Methyldopa used with haloperidol and chlorpromazine may produce psychomotor

retardation, memory impairment, and inability to concentrate.

12. Methyldopa used with monoaminoxidase inhibitor drugs may produce headache

and hypertension.

Adverse effects:

Main adverse effects those are associated--Sedation, headache, asthenia, drowsiness, depression, impaired mental acuity, impaired

ability to concentrate, lapses of memory, nightmares, nausea, dryness of the mouth, nasal

stuffiness, dizziness, vertigo, edema, disorders of sexual function, weight gain, orthostatichypotension with lightheadedness.

Dosage:

Loading dose: 250mg 2-3 times daily, for first 48hrs.Maintenance dose: 500mg twice daily

Toxic Dose: 7.5mg/kg

Overdose may produce coma, hypothermia, hypotension, bradycardia, dry mouth, andatrioventricular conduction.

■ No Antidote known.



Pharmaceutical Particulars:

List of Excipients:Also contains: polyvidone, sodium edetate, magnesium stearate, crospovidone,

precipitated silica, macrogol, talc, E104, E110, E132, E171, E172, E330, E460, E464.

Incompatibilities: None

Storage:

Store below 25°C in a dry place.

Protect from light.

Packing:

The product containers found suitable are—

Rigid injection moulded polypropylene or injection blow-moulded polyethylenecontainers and snap-on polyethylene lids.

The product may also be supplied in blister packs in cartons:

a) Carton: Printed carton manufactured from white folding box board.

b) Blister pack: (i) 250µm white rigid PVC. (ii) Surface printed 20µm hard temper

aluminium foil with 5-7g/M² PVC and PVdC compatible heat seal lacquer on thereverse side.

Few Branded formulations available:

Aldoclor 150, Aldoclor 250, Aldomet, Dopamet, Medomet, Medopal, Presinol

References:

■ http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=40175#x27

■ USP30-NF25 Page 2627■ http://www.medicinenet.com/methyldopa-oral/page2.htm

■ http://www.drugbank.ca/drugs/APRD01106

■ http://www.inchem.org/documents/pims/pharm/methyldo.htm■ http://www.drugbank.ca/drugs/DB00968#pharmacology■ https://online.epocrates.com/u/10a252/methyldopa■ http://www.medicines.org.uk/emc/medicine/24120/SPC/methyldopa%20tablets%

20bp%20125mg/#FORM

Documents

Methyl Dopa2