Anandamide pharmacology

Since the discovery of anandamide in 1992, a number of studies have examined its pharmacological properties. Although its roles are still elusive, a plethora of data supports the initial postulate that anandamide is the major endogenous cannabinoid ligand. As mentioned earlier, anandamide binds to CB1 from brain preparations and displaces various well-... 

Anandamide, in vivo, was shown to produce the four characteristic effects of cannabimimetics, namely, analgesia, hypothermia, hypoactiv-ity, and catalepsy (Smith, 1994 Fride, 1993 Crawley, 1993). These four effects are not unique to cannabimimetics when they are produced together, however, they are highly predictive of cannabimimetic activity (Martin, 1991). Anandamide was found to be less potent than delta-9-THC in producing these behavioral effects in mice (Fride, 1993). It has quicker onset and shorter duration of action, the latter because of rapid catabolism. Cross-tolerance studies, in which pretreatment of mice with delta-9-THC produced tolerance to most of the pharmacological effects of anandamide and vice versa, indicate that both drugs act on the same receptor (Jarbe, 1998). 

In addition, anandamide was found to parallel classical cannabinoid pharmacology in a series of nonbehavioral experimental systems. In isolated MVD, (Pertwee, 1992) and guinea pig ileum, it inhibited electrically evoked twitch responses (Pertwee, 1995). Moreover, anandamide was shown to decrease intraocular pressure in rabbits (Pate, 1995), to reduce sperm-fertilizing capacity in sea urchins by inhibition of the acrosome reaction (Schuel, 1994), and to produce hypotension in rats (Varga, 1995). 

All the foregoing pharmacological effects of anandamide, in conjunction with the well-documented existence of specific systems for its biosynthesis, catabolism, and cellular reuptake to be discussed shortly, suggest that anandamide is indeed the endogenous cannabinoid ligand. The other two less studied A -acylethanolamide endocannabinoids and also 2-AG may serve similar functions. The differential roles of each of these four endocannabinoids are still unclear. 

Fride E, Mechoulam R. Pharmacological activity of the cannabinoid receptor agonist, anandamide, a brain constituent. Eur J Pharmacol 1993 231 313-314. 

Smith PB, Compton DR, Welch SP, Razdan RK, Mechoulam R, Martin BR, The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice. J Pharmacol Exp Ther 1994 270 219-227. 

Anandamide inhibited the specific binding of [ H]-HU-243 to synaptosomal membranes in a manner typical of competitive ligands, with an inhibition constant (K ) of 39.0 + 5.0 nM. In this system, the of tsP-THC, a psychoactive compound of cannabis, was 46.0 + 3-0 nM. These were exciting results — the psychoactive compound from a higher plant and a chemically completely different compound in the brain were found to bind to the same brain receptor at about the same level of activity. Soon after the identification of anandamide, this compound was tested for its pharmacological activity. Anandamide administered i.p. in mice, caused... 

Why is that Why is chocolate the most frequently mentioned food in surveys about cravings (Actually, this is mostly true for young women men crave pizza.) While some scientists have argued that the cause Is certain compounds, such as anandamide or caffeine, which do have the potential for pharmacological activity, the consensus is that chocolate is addictive because of its flavor. Not its taste, however. Flavor is more than just taste smell and texture also come into play. Flavor chemist Dr. Sara Kisch proved this very effectively at the chocolate symposium. She handed out jelly beans of various flavors and asked us to sample them while holding our noses. They were indistinguishable. But identification was no problem once our nostrils were liberated. It was a dramatic demonstration of the role smells play in flavor detection. When the nose is pinched, no air can flow from the mouth to the nasal passage, where our... 

Pharmacological properties of anandamide - further evidence for an unknown cannabinoid receptor... 

As an example of the application of metabolomics, we will refer to the substrates of the enzyme fatty acyl amide hydrolase (FAAH) that regulates several brain lipids that have interesting pharmacological properties including effects on the control of pain. It is well known that some fatty acyl amides of ethanolamine are substrates of FAAH, such as the ethanolamide of arachidonic acid (anandamide), which is an endogenous ligand of cannabinoid receptors. 

Structurally there is little in common between A9-THC and anandamide. The cannabinoids are terpenophenols, while the anandamides are fatty acid derivatives. Yet, pharmacologically they have much in common. Both A9-THC and anandamide were shown to cause a typical tetrad of behavioural actions hypothermia, hypomotility, antinociception and catalepsy. In most behavioural tests, anandamide is somewhat less potent than d9-THC [35, 36]. Repeated injections of anandamide (i.p.) produced tolerance to a challenge with THC or anandamide. This tolerance however was less persistent than that commonly seen with THC, lasting for only one week [37],... 

Our group has looked at the problem from a different angle. We assumed that oleamide and anandamide may have common pharmacological fea-... 

Di Marzo V, Breivogel CS, Tao Q, Bridgen DT, Razdan RK, Zimmer AM, Zimmer A, Martin BR (2000b) Levels, metabolism, and pharmacological activity of anandamide in CBi cannabi-noid receptor knockout mice. Evidence for non-CBi, non-CBi receptor-mediated actions of anandamide in mouse brain. J Neurochem 75 2434-2444 Di Marzo V, Melck D, Bisogno T, De Petrocellis L (1998) Endocannabinoids endogenous cannabinoid receptor hgands with neuromodulatory action. Trends Neurosci 21 521-528 Dickinson T, Fleetwood-Walker SM (1999) VIP and PACAP very important in pain Trends Pharmacol Sci 20 324-329... 

Price TJ, Patwardhan A, Akopian AN, Hargreaves KM, Flores CM (2004) Modulation of trigeminal sensory neuron activity by the dual cannabinoid-vanilloid agonists anandamide, N-arachidonoyl-dopamine and arachidonyl-2-chloroethylamide. Br J Pharmacol 141 1118-1130 Proudfit HK (1988) Pharmacologic evidence for the modulation of nociception by noradrenergic neurons. Prog Brain Res 77 357-370... 

Wise LE, Shelton CC, Cravatt BE, Martin BR, Lichtman AH (2007) Assessment of anandamide s pharmacological effects in mice deficient of both fatty acid amide hydrolase and cannabinoid CBl receptors. Eur J Pharmacol 557 44-48... 

Arachidonic acid ethanolamide (anandamide) and similar compounds are constituents of the brain. Anandamide and certain of the compounds similar with same, bind to the cannabinoid receptor. The binding of the ananamide to the cannabinoid receptor is similar to the binding of A9-tetrahydrocannabinol. There exist in the body many mediators, which are derivatives of arachidonic acid, such as prostaglandins and leukotrienes, which are present as large families of related compounds. Certain of these do not bind to the cannabinoid receptor, and it was one of the aims of the present invention to provide and identify compounds which have pharmacological properties similar to the properties of anandamide. 

Endogenous ligands for the cannabinoid receptor have not yet been identified. Arachidonylethanolamide, a new arachidonic acid derivative named anandamide, was isolated from porcine brain. Its structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy and was confirmed by synthesis. It inhibits the specific binding of a labelled cannabinoid probe to synaptosomal membranes in a manner typical of competitive ligands, and produces a concentration-dependent inhibition of the electrically-evoked twitch response of the mouse vas deferens, a characteristic effect of psychotropic cannabinoids. Similar compounds were synthesized and their pharmacological properties were investigated. 

Arachidonyl ethanolamide (anandamide) is a naturally-occurring brain constituent that acts as a CBl and CB2 agonist and exhibits pharmacological activity in mice comparable to cannahinoids (Fride and Mechoulam (1993), Crawley et al. (1993) and Smith et al. (1994)). Anandamide is cleaved in vivo by anandamide amidase. Thus, inhibitors of anandamide amidase have the effect of indirectly stimulating the CBl and CB2 receptors by increasing in vivo levels of anandamide. In addition to acting at the CBl and CB2 receptors, cannahinoids also affect cellular membranes, thereby producing undesirable side effects... 

Deutsch, D. G. and Chin, S. A., Enzymatic Synthesis and Degradation of Anandamide, A Cannabinoid Receptor Agonist, Biochemical Pharmacology, 46(5) 791-796 (1993). 

Smith, P. B., et al.. The Pharmacological Activity of Anandamide, a Putative Endogenous Cannabinoid, in Mice, The Journal of Pharmacology and Experimental Therapeutics, 270 (1) 219-227 (1994). 

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