What is the mechanism of action (MOA) and pharmacokinetics (PK) of pink cocaine, also known as 2,5-dimethoxy-4-methylamphetamine or Methyl​enedioxy​pyrovalerone (MDPV)?

From the Guidelines

Pink cocaine, also known as 2,5-dimethoxy-4-methylamphetamine or Methyl​enedioxy​pyrovalerone (MDPV), is a synthetic drug with a mechanism of action that involves multiple neurotransmitter systems, but its exact MOA and PK are not well-defined in the provided evidence. The provided evidence primarily discusses the effects of cocaine, which is a different substance from pink cocaine. However, it can be inferred that pink cocaine may have similar stimulant effects due to its potential composition of substances like methamphetamine.

Mechanism of Action (MOA)

• The MOA of pink cocaine is not explicitly stated in the provided evidence, but it is likely to involve the inhibition of catecholamine reuptake, leading to increased levels of dopamine, norepinephrine, and serotonin in the brain, similar to other stimulant substances 1.
• The evidence suggests that cocaine, a different substance, produces a sympathomimetic toxidrome marked by tachycardia, hypertension, hyperthermia, seizures, diaphoresis, increased psychomotor activity, and cocaine induces tachycardia (postsynaptic β-adrenergic receptor agonism) and hypertension (peripheral postsynaptic α-adrenergic receptor agonism) by catecholamine reuptake inhibition 1.

Pharmacokinetics (PK)

• The PK of pink cocaine is not well-defined in the provided evidence, but it is likely to have a rapid onset of action and a variable duration of effects depending on the specific components and route of administration.
• The evidence suggests that the treatment of cocaine-induced toxicity involves the use of benzodiazepines, calcium channel blockers, and other agents to control hypertension, tachycardia, and agitation 1. In summary, the exact MOA and PK of pink cocaine are not well-defined, but it is likely to involve the inhibition of catecholamine reuptake and have a rapid onset of action with variable effects, and treatment should focus on controlling symptoms and preventing complications, as suggested by the evidence on cocaine toxicity 1.

From the Research

Mechanism of Action (MOA)

• Synthetic cathinones, including 2,5-dimethoxy-4-methylamphetamine and Methyl​enedioxy​pyrovalerone (MDPV), produce their actions primarily via the dopamine, norepinephrine, and/or serotonin transporter 2
• They either release and/or inhibit the reuptake of one or more of these neurotransmitters, leading to increased extracellular monoamine concentrations in the brain 3
• Ring-substituted cathinones like mephedrone are transporter substrates that evoke neurotransmitter release by reversing the normal direction of transporter flux (i.e., releasers) 3
• Pyrrolidine-containing cathinones like 3,4-methylenedioxypyrovalerone (MDPV) are potent transporter inhibitors that block neurotransmitter uptake (i.e., blockers) 3

Pharmacokinetics (PK)

• There is limited information available on the pharmacokinetics of pink cocaine, also known as 2,5-dimethoxy-4-methylamphetamine or Methyl​enedioxy​pyrovalerone (MDPV)
• However, it is known that synthetic cathinones are rapidly absorbed and distributed throughout the body, leading to rapid onset of effects 4, 5
• The exact pharmacokinetic parameters of pink cocaine, such as its half-life, metabolism, and elimination, are not well established and require further research

Clinical Effects

• Synthetic cathinones, including pink cocaine, can produce a range of clinical effects, including sympathicomimetic toxidrome, agitation, psychosis, tachycardia, hypertension, and seizures 6, 4
• They can also lead to more severe effects, such as excited delirium, dehydration, skeletal muscle damage, and renal failure, which can be life-threatening 4, 5