CHEMISTRY AND BIOLOGICAL ACTIONS
Ephedrine	Forskolin
Chemically, ephedrine found in herbs such as Ma Huang (Ephedra sinica) is a phenylethylamine compound structurally similar to amphetamine, belonging to the class of sympathomimetic protoalkaloids1Sympathomimetic compounds mimic the action of adrenaline (epinephrine)-like neuro-transmitters at peripheral sympathetic neurons and also exert central nervous system effects.Adrenaline systems control important body functions like blood pressure regulation and wakefulness.Ephedrine has a1 a2 b1 b2 adrenergic receptor-agonist properties3. 40% of the thermogenic activity of ephedrine is reported to be due to the activation of the b3 adrenoreceptors in the adipose tissues2. Ephedrine also stimulates thyroid functions. Ephedrine is referred to as a mixed-acting drug because it activates adrenergic receptors by direct and indirect mechanisms. Direct activation results from binding of the drug to alpha and beta-receptors. Indirect activation results from release of noradrenaline from adrenergic neurons3.	Chemically, forskolin found in Coleus forskohlii is a labdane diterpene1.It is a direct activator of the enzyme adenylate cyclase which is involved in the generation of cyclic adenosine monophosphate (cAMP)4. Forskolin also stimulates thyroid functions.cAMP is a “second messenger” hormone signaling system. In many hormone sensitive systems the hormone itself does not enter the target cell, but binds to a receptor and indirectly affects the production of another molecule within the cell, which then diffuses intracellularly to the target enzymes or a receptor inside the cell to produce the response. This intracellular mediator is called the second messenger.cAMP, and therefore forskolin, have marked physiological effects through such “second messenger” actions on various biochemical processes in the body.
Mechanism of thermogenic action and its significance
Significance
activation of hormone sensitive lipase is linked to cAMP Forskolin bypasses the adrenergic receptors activation step, increasing cAMP levels directly. The beneficial effects of forskolin, therefore, do not depend upon the sensitivity of the adrenergic receptors which can often decrease with age and other physiological factors. forskolin has also been shown to counteract the decreased response of fat cells to epinephrine, associated with aging. The mechanism of action of forskolin does not involve non-selective binding to the adrenergic receptors. Therefore, forskolin does not produce the unwanted side effects associated with their activation.
Ephedrine	Forskolin
Since ephedrine activates the same adrenergic receptors as epinephrine, these drugs share the same adverse effects3.Hypertension (increase in blood pressure), due to constriction of the peripheral blood vessels (vasoconstriction)Dysrhythmias (increased heart rate due to cardiac stimulation)Angina (chest pain due to depleted oxygen in the heart muscle) Hyperglycemia (increase in blood sugar levels) Ephedrine use is therefore contraindicated in people prone to hypertension, heart disease, hyperglycemia, hyper- thyroidism, prostate disease and related conditions and in those taking prescription medications3,6. Care should be taken to avoid administration of ephedrine with other stimulants such as caffeine7.	The mechanism of action of forskolin does not entail the activation of adrenergic receptors.Forskolin is a known blood pressure lowering agent and is used in the management of hypertension, including ocular hypertension that leads to glaucoma4.Preliminary studies in humans have shown that forskolin increases the contractility of the heart muscle without increasing oxygen consumption and that it is a vasodilator4,8.Forskolin has been shown to inhibit platelet aggregation further validating its beneficial cardiovascular effects9. Forskolin is known to regulate the secretion of insulin, thereby helping to maintain healthy blood sugar levels11. As with all other supplements, people taking medications for asthma, hypertension, hyperthyroidism and related conditions as well as those suffering from ulcers or low blood pressure conditions should exercise caution13 and seek medical supervision.

Reference

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2. Liu, Y.L. et al. (1995) Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans. Int J Obes Relat Metab Disord. 19(9):678-85
3. Prives, J. Autonomic Neuropharmacology III
4. Ammon, H.P.T. and Muller (1989) Forskohlin: from an Ayurvedic Remedy to a Modern Agent Planta Medica. Vol 51, 475- 476.
5. Allen, D.O. et al. (1986) Relationships between cyclic AMP levels and lipolysis in fat cells after isoproterenol and forskohlin stimulation. The Journal of Pharmacology and Experimental Therapeutics. 238(2): 659-664.
6. Gurley, B.J. et al (1998) Ephedrine pharmacokinetics after ingestion of nutritional supplements containing Ephedra sinica (ma huang). Therapeutic Drug Monitoring 20, 439-445.
7. Weesner, K.M. et al. (1982) Cardiac arrhythmias in an adolescent following ingestion of an over-the-counter stimulant. Clin. Pediatr. (Phila.) 21, 700-701.
8. Rupp, R.H. et al. ed. (1985) Forskohlin: Its chemical biological and medical potential. Proc of the International Symposium, Hoechst India Ltd, Bombay.
9. Lindner E, et al. (1978): Positive inotropic and blood pressure lowering activity of a diterpene derivative isolated form Coleus forskohlii: forskolin. Arzneim.-Forsch 28:284-9.
10. Research Report, Sabinsa Corporation, 1999.
11. Yajima H. et al (1999) cAMP enhances insulin secretion by an action on the ATP-sensitive K+ channel-independent pathway of glucose signaling in rat pancreatic islets. Diabetes 48(5):1006-12
12. Research Report, Sabinsa Corporation, 2000. MB Research Laboratories.
13. American Botanical Council. Coleus Forskohlii Monograph. HerbClip May 1, 1997.